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Emerging therapeutic frontiers in cancer: insights into posttranslational modifications of PD-1/PD-L1 and regulatory pathways Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-04-23 Rong Wang, Shiwei He, Jun Long, Yian Wang, Xianjie Jiang, Mingfen Chen, Jie Wang
The interaction between programmed cell death ligand 1 (PD-L1), which is expressed on the surface of tumor cells, and programmed cell death 1 (PD-1), which is expressed on T cells, impedes the effective activation of tumor antigen-specific T cells, resulting in the evasion of tumor cells from immune-mediated killing. Blocking the PD-1/PD-L1 signaling pathway has been shown to be effective in preventing
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Exploring the role of histone deacetylase and histone deacetylase inhibitors in the context of multiple myeloma: mechanisms, therapeutic implications, and future perspectives Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-04-23 Jingjing Pu, Ting Liu, Xuzhen Wang, Amit Sharma, Ingo G. H. Schmidt-Wolf, Liping Jiang, Jian Hou
Histone deacetylase inhibitors (HDACis) are a significant category of pharmaceuticals that have developed in the past two decades to treat multiple myeloma. Four drugs in this category have received approval from the U.S. Food and Drug Administration (FDA) for use: Panobinonstat (though canceled by the FDA in 2022), Vorinostat, Belinostat and Romidepsin. The efficacy of this group of drugs is attributed
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Novel agents and regimens in relapsed or refractory peripheral T-cell lymphoma: latest updates from 2023 ASH annual meeting Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-04-22 Huageng Huang, Wei Zhang, Xinyi Deng, He Huang, Zhao Wang, Huangming Hong, Tongyu Lin
Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of hematological malignancies with poor survival, while treatment options for relapsed or refractory (R/R) disease remain quite limited, with a median progression-free survival of only 3–4 months. Notably, the emergence of innovative therapeutic agents and regimens holds promise for durable responses and improved survival for patients with
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Novel CAR T-cell therapies for relapsed/refractory B-cell malignancies: latest updates from 2023 ASH annual meeting Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-04-18 Wenjie Zhang, Sumei Li, Jinlan Long, Shufeng Xie, Minghui Wang, Han Liu, Zhenshu Xu
Chimeric antigen receptors (CAR) are engineered fusion proteins that target T-cells to specific surface antigens of tumor cells to generate effective anti-tumor responses. CAR T-cell therapy is playing an increasingly important role in the treatment of relapsed/refractory B-cell malignancies (R/R BCM). Attempting to make CAR T-cells safer and more effective in treating R/R BCM, various novel engineered
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Pan-cancer transcriptional atlas of minimal residual disease links DUSP1 to chemotherapy persistence Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-04-16 Yuanhui Liu, Bi Peng, Ziqi Chen, Yimin Shen, Jingmin Zhang, Xianglin Yuan
Chemotherapy is a commonly effective treatment for most types of cancer. However, many patients experience a relapse due to minimal residual disease (MRD) after chemotherapy. Previous studies have analyzed the changes induced by chemotherapy for specific types of cancer, but our study is the first to comprehensively analyze MRD across various types of cancer. We included both bulk and single-cell RNA
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A Fab of trastuzumab to treat HER2 overexpressing breast cancer brain metastases Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-04-15 Eurydice Angeli, Justine Paris, Olivier Le Tilly, Céline Desvignes, Guillaume Gapihan, Didier Boquet, Frédéric Pamoukdjian, Diaddin Hamdan, Marthe Rigal, Florence Poirier, Didier Lutomski, Feriel Azibani, Alexandre Mebazaa, Amaury Herbet, Aloïse Mabondzo, Géraldine Falgarone, Anne Janin, Gilles Paintaud, Guilhem Bousquet
Despite major therapeutic advances for two decades, including the most recently approved anti-HER2 drugs, brain metastatic localizations remain the major cause of death for women with metastatic HER2 breast cancer. The main reason is the limited drug passage of the blood-brain barrier after intravenous injection and the significant efflux of drugs, including monoclocal antibodies, after administration
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Mechanistic insights and the clinical prospects of targeted therapies for glioblastoma: a comprehensive review Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-04-13 Yating Shen, Dexter Kai Hao Thng, Andrea Li Ann Wong, Tan Boon Toh
Glioblastoma (GBM) is a fatal brain tumour that is traditionally diagnosed based on histological features. Recent molecular profiling studies have reshaped the World Health Organization approach in the classification of central nervous system tumours to include more pathogenetic hallmarks. These studies have revealed that multiple oncogenic pathways are dysregulated, which contributes to the aggressiveness
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Myeloid-derived suppressor cells in cancer: therapeutic targets to overcome tumor immune evasion Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-04-12 Junli Lu, Yiming Luo, Dean Rao, Tiantian Wang, Zhen Lei, Xiaoping Chen, Bixiang Zhang, Yiwei Li, Bifeng Liu, Limin Xia, Wenjie Huang
Paradoxically, tumor development and progression can be inhibited and promoted by the immune system. After three stages of immune editing, namely, elimination, homeostasis and escape, tumor cells are no longer restricted by immune surveillance and thus develop into clinical tumors. The mechanisms of immune escape include abnormalities in antitumor-associated immune cells, selection for immune resistance
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TRIB3 silencing promotes the downregulation of Akt pathway and PAX3-FOXO1 in high-risk rhabdomyosarcoma Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-04-05 Gabriel Gallo-Oller, Guillem Pons, Júlia Sansa-Girona, Natalia Navarro, Patricia Zarzosa, Lia García-Gilabert, Paula Cabré-Fernandez, Gabriela Guillén Burrieza, Lorena Valero-Arrese, Miguel F. Segura, José M. Lizcano, José Sánchez de Toledo, Lucas Moreno, Soledad Gallego, Josep Roma
Rhabdomyosarcoma (RMS), such as other childhood tumors, has witnessed treatment advancements in recent years. However, high-risk patients continue to face poor survival rates, often attributed to the presence of the PAX3/7-FOXO1 fusion proteins, which has been associated with metastasis and treatment resistance. Despite efforts to directly target these chimeric proteins, clinical success remains elusive
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Novel insights into TCR-T cell therapy in solid neoplasms: optimizing adoptive immunotherapy Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-04-03 Weihuan Shao, Yiran Yao, Ludi Yang, Xiaoran Li, Tongxin Ge, Yue Zheng, Qiuyi Zhu, Shengfang Ge, Xiang Gu, Renbing Jia, Xin Song, Ai Zhuang
Adoptive immunotherapy in the T cell landscape exhibits efficacy in cancer treatment. Over the past few decades, genetically modified T cells, particularly chimeric antigen receptor T cells, have enabled remarkable strides in the treatment of hematological malignancies. Besides, extensive exploration of multiple antigens for the treatment of solid tumors has led to clinical interest in the potential
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Vaccination with a combination of STING agonist-loaded lipid nanoparticles and CpG-ODNs protects against lung metastasis via the induction of CD11bhighCD27low memory-like NK cells Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-03-29 Alaa M. Khalifa, Takashi Nakamura, Yusuke Sato, Hideyoshi Harashima
Natural killer (NK) cells are effective in attacking tumor cells that escape T cell attack. Memory NK cells are believed to function as potent effector cells in cancer immunotherapy. However, knowledge of their induction, identification, and potential in vivo is limited. Herein, we report on the induction and identification of memory-like NK cells via the action of a combination of a stimulator of
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VISTA drives macrophages towards a pro-tumoral phenotype that promotes cancer cell phagocytosis yet down-regulates T cell responses Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-03-29 Yusheng Lin, Ghizlane Choukrani, Lena Dubbel, Lena Rockstein, Jimena Alvarez Freile, Yuzhu Qi, Valerie Wiersma, Hao Zhang, Karl-Wilhelm Koch, Emanuele Ammatuna, Jan Jacob Schuringa, Tom van Meerten, Gerwin Huls, Edwin Bremer
VISTA is a well-known immune checkpoint in T cell biology, but its role in innate immunity is less established. Here, we investigated the role of VISTA on anticancer macrophage immunity, with a focus on phagocytosis, macrophage polarization and concomitant T cell activation. Macrophages, differentiated from VISTA overexpressed THP-1 cells and cord blood CD34+ cell-derived monocytes, were used in phagocytosis
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Cyclin dependent kinase 4/6 inhibitor palbociclib synergizes with BCL2 inhibitor venetoclax in experimental models of mantle cell lymphoma without RB1 deletion Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-03-25 Diana Malarikova, Radek Jorda, Kristyna Kupcova, Jana Senavova, Alexandra Dolnikova, Eva Pokorna, Dmitry Kazantsev, Kristina Nozickova, Dana Sovilj, Celine Bellanger, David Chiron, Ladislav Andera, Vladimir Krystof, Miroslav Strnad, Karel Helman, Magdalena Klanova, Marek Trneny, Ondrej Havranek, Pavel Klener
Mantle cell lymphoma (MCL) is a chronically relapsing malignancy with deregulated cell cycle progression. We analyzed efficacy, mode of action, and predictive markers of susceptibility to palbociclib, an approved CDK 4/6 inhibitor, and its combination with venetoclax, a BCL2 inhibitor. A panel of nine MCL cell lines were used for in vitro experiments. Four patient derived xenografts (PDX) obtained
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Heat-killed Prevotella intermedia promotes the progression of oral squamous cell carcinoma by inhibiting the expression of tumor suppressors and affecting the tumor microenvironment Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-03-21 Yifan Zhou, Yao Qin, Jingjing Ma, Zhiyuan Li, Weiwei Heng, Lei Zhang, Hong Liu, Ruowei Li, Miaomiao Zhang, Qiao Peng, Pei Ye, Ning Duan, Ting Liu, Wenmei Wang, Xiang Wang
Oral microbial dysbiosis contributes to the development of oral squamous cell carcinoma (OSCC). Our previous study showed that Prevotella intermedia (P. intermedia) were enriched in the oral mucosal surface, plaque, and saliva of patients with OSCC. Intratumoral microbiome could reshape the immune system and influence the development of various tumors. However, the invasion status of human OSCC tissues
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Ubiquitin ligase subunit FBXO9 inhibits V-ATPase assembly and impedes lung cancer metastasis Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-03-14 Liang Liu, Xiaodong Chen, Leilei Wu, Kaizong Huang, Zhenyi Wang, Yaolin Zheng, Cheng Zheng, Zhenshan Zhang, Jiayan Chen, Jiaming Wei, Song Chen, Weilin Jin, Jinfei Chen, Dongping Wei, Yaping Xu
The evolutionarily conserved protein FBXO9 acts as a substrate receptor for the SKP1-cullin-1-RBX1 ubiquitin ligase and is implicated in cancer, exhibiting either tumor-suppressive or oncogenic effects depending on the specific tumor type. However, their role in lung cancer metastasis remains unclear. Lentiviral vectors carrying miRNA-based shRNA sequences for gene-specific knockdown were generated
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Harnessing ferroptosis for enhanced sarcoma treatment: mechanisms, progress and prospects Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-03-12 Jing Zeng, Xianghong Zhang, Zhengjun Lin, Yu Zhang, Jing Yang, Pengcheng Dou, Tang Liu
Sarcoma is a malignant tumor that originates from mesenchymal tissue. The common treatment for sarcoma is surgery supplemented with radiotherapy and chemotherapy. However, patients have a 5-year survival rate of only approximately 60%, and sarcoma cells are highly resistant to chemotherapy. Ferroptosis is an iron-dependent nonapoptotic type of regulated programmed cell death that is closely related
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Suppression of A-to-I RNA-editing enzyme ADAR1 sensitizes hepatocellular carcinoma cells to oxidative stress through regulating Keap1/Nrf2 pathway Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-03-11 Houhong Wang, Xiaoyu Wei, Lu Liu, Junfeng Zhang, Heng Li
A-to-I RNA editing is an abundant post-transcriptional modification event in hepatocellular carcinoma (HCC). Evidence suggests that adenosine deaminases acting on RNA 1 (ADAR1) correlates to oxidative stress that is a crucial factor of HCC pathogenesis. The present study investigated the effect of ADAR1 on survival and oxidative stress of HCC, and underlying mechanisms. ADAR1 expression was measured
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MSCsDB: a database of single-cell transcriptomic profiles and in-depth comprehensive analyses of human mesenchymal stem cells Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-03-06 Miao Yu, Ke Sui, Zheng Wang, Xi Zhang
Mesenchymal stem cells (MSCs) possess multipotent properties that make them promising candidates for immunomodulation and regenerative medicine. However, MSC heterogeneity poses challenges to their research reproducibility and clinical application. The emergence of single-cell RNA sequencing (scRNA-seq) technology has enabled a thorough examination of MSC heterogeneity, underscoring the necessity for
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Cytokine-based models for efficient differentiation between infection and cytokine release syndrome in patients with hematological malignancies Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-03-05 Linqin Wang, Yuqi Lv, Linghui Zhou, Shenghao Wu, Yuanyuan Zhu, Shan Fu, Shuyi Ding, Ruimin Hong, Mingming Zhang, Hanjing Yu, Alex H. Chang, Guoqing Wei, Yongxian Hu, He Huang
Although the efficacy of chimeric antigen receptor (CAR)-T cell therapy has been widely demonstrated, its clinical application is hampered by the complexity and fatality of its side effects. Cytokine release syndrome (CRS) is the most common toxicity following CAR-T cell infusion, and its symptoms substantially overlap with those of infection. Whereas, current diagnostic techniques for infections are
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The multi-CDK inhibitor dinaciclib reverses bromo- and extra-terminal domain (BET) inhibitor resistance in acute myeloid leukemia via inhibition of Wnt/β-catenin signaling Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-03-04 Alexander R. Marr, Madeline Halpin, Dominique L. Corbin, Yerdanos Asemelash, Steven Sher, Britten K. Gordon, Ethan C. Whipp, Shaneice Mitchell, Bonnie K. Harrington, Shelley Orwick, Samon Benrashid, Virginia M. Goettl, Vedat Yildiz, Andrew D. Mitchell, Olivia Cahn, Alice S. Mims, Karilyn T. M. Larkin, Meixao Long, James Blachly, Jennifer A. Woyach, Rosa Lapalombella, Nicole R. Grieselhuber
Acute myeloid leukemia (AML) is a highly aggressive hematologic cancer with poor survival across a broad range of molecular subtypes. Development of efficacious and well-tolerable therapies encompassing the range of mutations that can arise in AML remains an unmet need. The bromo- and extra-terminal domain (BET) family of proteins represents an attractive therapeutic target in AML due to their crucial
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Drug conjugates for the treatment of lung cancer: from drug discovery to clinical practice Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-03-01 Ling Zhou, Yunlong Lu, Wei Liu, Shanglong Wang, Lingling Wang, Pengdou Zheng, Guisha Zi, Huiguo Liu, Wukun Liu, Shuang Wei
A drug conjugate consists of a cytotoxic drug bound via a linker to a targeted ligand, allowing the targeted delivery of the drug to one or more tumor sites. This approach simultaneously reduces drug toxicity and increases efficacy, with a powerful combination of efficient killing and precise targeting. Antibody‒drug conjugates (ADCs) are the best-known type of drug conjugate, combining the specificity
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Dual-targeted CAR T-cell immunotherapies for hematological malignancies: latest updates from the 2023 ASH annual meeting Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-27 Jingyi Yang, Hao Guo, Lu Han, Yongping Song, Keshu Zhou
Over the past few years, dual-targeted chimeric antigen receptor (CAR) T-cell therapy has been employed in the management of hematological malignancies to mitigate treatment failure, particularly in cases of antigen escape. The most widely used approaches include CD19/CD20, CD20/CD22, and BCMA/CD19 CAR T-cells. Alternative immune cells, including natural killer T cells and invariant natural killer
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The abundance of the short GATA1 isoform affects megakaryocyte differentiation and leukemic predisposition in mice Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-26 Daishi Ishihara, Atsushi Hasegawa, Ikuo Hirano, James Douglas Engel, Masayuki Yamamoto, Ritsuko Shimizu
Transcription factor GATA1 controls the delicate balance between proliferation, differentiation and apoptosis in both the erythroid and megakaryocytic lineages. In addition to full-length GATA1, there is an GATA1 isoform, GATA1s, that lacks the amino-terminal transactivation domain. Somatic GATA1 mutations that lead to the exclusive production of GATA1s appear to be necessary and sufficient for the
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Strain-dependent modifiers exacerbate familial leukemia caused by GATA1-deficiency Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-26 Ikuo Hirano, Kanako Abe, James Douglas Engel, Masayuki Yamamoto, Ritsuko Shimizu
GATA1 plays a critical role in differentiation, proliferation, and apoptosis during erythropoiesis. We developed a Gata1 knock-down allele (Gata1.05) that results in GATA1 expression at 5% of endogenous level. In female mice heterozygous for both the Gata1.05 and wild-type alleles, we observed a predisposition to erythroblastic leukemia three to six months after birth. Since no male Gata1.05 progeny
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Challenges and strategies associated with CAR-T cell therapy in blood malignancies Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-24 Zhaoyun Liu, Wenhui Lei, Hao Wang, Xiaohan Liu, Rong Fu
Cellular immunotherapy, particularly CAR-T cells, has shown potential in the improvement of outcomes in patients with refractory and recurrent malignancies of the blood. However, achieving sustainable long-term complete remission for blood cancer remains a challenge, with resistance and relapse being expected outcomes for many patients. Although many studies have attempted to clarify the mechanisms
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Targeting natural killer cells: from basic biology to clinical application in hematologic malignancies Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-23 Juanjuan Shang, Shunfeng Hu, Xin Wang
Natural killer (NK) cell belongs to innate lymphoid cell family that contributes to host immunosurveillance and defense without pre-immunization. Emerging studies have sought to understand the underlying mechanism behind NK cell dysfunction in tumor environments, and provide numerous novel therapeutic targets for tumor treatment. Strategies to enhance functional activities of NK cell have exhibited
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Cirrhotic-extracellular matrix attenuates aPD-1 treatment response by initiating immunosuppressive neutrophil extracellular traps formation in hepatocellular carcinoma Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-22 Xiao-Tian Shen, Sun-Zhe Xie, Xin Zheng, Tian-Tian Zou, Bei-Yuan Hu, Jing Xu, Lu Liu, Yun-Feng Xu, Xu-Feng Wang, Hao Wang, Shun Wang, Le Zhu, Kang-Kang Yu, Wen-Wei Zhu, Lu Lu, Ju-Bo Zhang, Jin-Hong Chen, Qiong-Zhu Dong, Lu-Yu Yang, Lun-Xiu Qin
Hepatocellular carcinoma (HCC) is closely associatedwith chronic liver diseases, particularly liver cirrhosis, which has an altered extracellular matrix (ECM) composition. The influence and its mechanism of the cirrhotic-ECM on the response of HCC to immune checkpoint inhibitor (ICI) remains less clarified. In silico, proteomic and pathological assessment of alteration of cirrhotic-ECM were applied
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Low-dose hypomethylating agents cooperate with ferroptosis inducers to enhance ferroptosis by regulating the DNA methylation-mediated MAGEA6-AMPK-SLC7A11-GPX4 signaling pathway in acute myeloid leukemia Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-20 Shuya Feng, Yigang Yuan, Zihan Lin, Min Li, Daijiao Ye, Liuzhi Shi, Danyang Li, Min Zhao, Chen Meng, Xiaofei He, Shanshan Wu, Fang Xiong, Siyu Ye, Junjun Yang, Haifeng Zhuang, Lili Hong, Shenmeng Gao
Ferroptosis is a new form of nonapoptotic and iron-dependent type of cell death. Glutathione peroxidase-4 (GPX4) plays an essential role in anti-ferroptosis by reducing lipid peroxidation. Although acute myeloid leukemia (AML) cells, especially relapsed and refractory (R/R)-AML, present high GPX4 levels and enzyme activities, pharmacological inhibition of GPX4 alone has limited application in AML.
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Blockade of the lncRNA-DOT1L-LAMP5 axis enhances autophagy and promotes degradation of MLL fusion proteins Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-19 Tian-Qi Chen, Heng-Jing Huang, Shun-Xin Zhu, Xiao-Tong Chen, Ke-Jia Pu, Dan Wang, Yan An, Jun-Yi Lian, Yu-Meng Sun, Yue-Qin Chen, Wen-Tao Wang
Mixed-lineage leukemia (MLL) fusion gene caused by chromosomal rearrangement is a dominant oncogenic driver in leukemia. Due to having diverse MLL rearrangements and complex characteristics, MLL leukemia treated by currently available strategies is frequently associated with a poor outcome. Therefore, there is an urgent need to identify novel therapeutic targets for hematological malignancies with
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Venetoclax-based therapy for relapsed or refractory acute myeloid leukemia: latest updates from the 2023 ASH annual meeting Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-16 Xubo Gong, Xin He, Lin Wang, Teng Yu, Weiwei Liu, Huiying Xu, Lan Jin, Xiang Li, Bin Zhang, Zhihua Tao, Wenbin Qian
Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) often exhibit limited responses to traditional chemotherapy, resulting in poor prognosis. The combination of venetoclax (VEN) with hypomethylating agents has been established as the standard treatment for elderly or medically unfit AML patients unable to undergo intensive chemotherapy. Despite this, the availability of novel VEN-based
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Outcomes of acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: validation, comparison and improvement of 2022 ELN genetic risk system Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-15 Haixiao Zhang, Xinhui Zheng, Wenwen Guo, Yonghui Xia, Rongli Zhang, Weihua Zhai, Xin Chen, Qiaoling Ma, Donglin Yang, Jialin Wei, Aiming Pang, Yi He, Sizhou Feng, Jianxiang Wang, Mingzhe Han, Erlie Jiang
The 2022 European LeukemiaNet (ELN) updated the previous risk classification published in 2017 but the prognostic significance for allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We enrolled 600 acute myeloid leukemia (AML) patients who underwent allo-HSCT to validate ELN-2022 genetic risk system and compared it with ELN-2017. There were 214 (35.67%), 162 (27.0%), and
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Revealing the role of the gut microbiota in enhancing targeted therapy efficacy for lung adenocarcinoma Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-09 Ting Jiang, Meng Zhang, Shaoyu Hao, Shi Huang, Xin Zheng, Zheng Sun
Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death globally. Although the gut microbiota's role in the antitumor efficacy of many cancers has been revealed, its involvement in the response to gefitinib therapy for LUAD remains unclear. To fill this gap, we conducted a longitudinal study that profiled gut microbiota changes in PC-9 tumor-bearing mice under different treatments,
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The HSP90-MYC-CDK9 network drives therapeutic resistance in mantle cell lymphoma Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-02-07 Fangfang Yan, Vivian Jiang, Alexa Jordan, Yuxuan Che, Yang Liu, Qingsong Cai, Yu Xue, Yijing Li, Joseph McIntosh, Zhihong Chen, Jovanny Vargas, Lei Nie, Yixin Yao, Heng-Huan Lee, Wei Wang, JohnNelson R. Bigcal, Maria Badillo, Jitendra Meena, Christopher Flowers, Jia Zhou, Zhongming Zhao, Lukas M. Simon, Michael Wang
Brexucabtagene autoleucel CAR-T therapy is highly efficacious in overcoming resistance to Bruton’s tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma. However, many patients relapse post CAR-T therapy with dismal outcomes. To dissect the underlying mechanisms of sequential resistance to BTKi and CAR-T therapy, we performed single-cell RNA sequencing analysis for 66 samples from 25 patients treated
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GPR68-ATF4 signaling is a novel prosurvival pathway in glioblastoma activated by acidic extracellular microenvironment Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-31 Charles H. Williams, Leif R. Neitzel, Jessica Cornell, Samantha Rea, Ian Mills, Maya S. Silver, Jovanni D. Ahmad, Konstantin G. Birukov, Anna Birukova, Henry Brem, Betty Tyler, Eli E. Bar, Charles C. Hong
Glioblastoma multiforme (GBM) stands as a formidable challenge in oncology because of its aggressive nature and severely limited treatment options. Despite decades of research, the survival rates for GBM remain effectively stagnant. A defining hallmark of GBM is a highly acidic tumor microenvironment, which is thought to activate pro-tumorigenic pathways. This acidification is the result of altered
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Decoding leukemia at the single-cell level: clonal architecture, classification, microenvironment, and drug resistance Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-30 Jianche Liu, Penglei Jiang, Zezhen Lu, Zebin Yu, Pengxu Qian
Leukemias are refractory hematological malignancies, characterized by marked intrinsic heterogeneity which poses significant obstacles to effective treatment. However, traditional bulk sequencing techniques have not been able to effectively unravel the heterogeneity among individual tumor cells. With the emergence of single-cell sequencing technology, it has bestowed upon us an unprecedented resolution
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Targeting focal adhesion kinase boosts immune response in KRAS/LKB1 co-mutated lung adenocarcinoma via remodeling the tumor microenvironment Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-30 Meng Qiao, Fei Zhou, Xinyu Liu, Tao Jiang, Haowei Wang, Xuefei Li, Chao Zhao, Lei Cheng, Xiaoxia Chen, Shengxiang Ren, Zaiqi Wang, Caicun Zhou
KRAS mutation is one of the most common oncogenic drivers in NSCLC, however, the response to immunotherapy is heterogeneous owing to the distinct co-occurring genomic alterations. KRAS/LKB1 co-mutated lung adenocarcinoma displays poor response to PD-1 blockade whereas the mechanism remains undetermined. We explored the specific characteristics of tumor microenvironment (TME) in KL tumors using syngeneic
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Cancer metabolism and carcinogenesis Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-29 Jianqiang Yang, Chloe Shay, Nabil F. Saba, Yong Teng
Metabolic reprogramming is an emerging hallmark of cancer cells, enabling them to meet increased nutrient and energy demands while withstanding the challenging microenvironment. Cancer cells can switch their metabolic pathways, allowing them to adapt to different microenvironments and therapeutic interventions. This refers to metabolic heterogeneity, in which different cell populations use different
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A novel AML1-ETO/FTO positive feedback loop promotes leukemogenesis and Ara-C resistance via stabilizing IGFBP2 in t(8;21) acute myeloid leukemia Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-24 Wei Zhou, Siying Li, Hong Wang, Jingfeng Zhou, Shuyi Li, Guofeng Chen, Wei Guan, Xianli Fu, Clara Nervi, Li Yu, Yonghui Li
t(8;21)(q22;q22) is one of the most frequent chromosomal abnormalities in acute myeloid leukemia (AML), leading to the generation of the fusion protein AML1-ETO. Despite t(8;21) AML being considered as a subtype with a favorable prognosis, approximately 30–50% of patients experience drug resistance and subsequent relapse. N6-methyladenosine (m6A) is demonstrated to be involved in the development of
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METTL1 mediated tRNA m7G modification promotes leukaemogenesis of AML via tRNA regulated translational control Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-24 Pan Zhao, Lin Xia, Dan Chen, Wei Xu, Huanping Guo, Yinying Xu, Bingbing Yan, Xiao Wu, Yuxia Li, Yunfang Zhang, Xi Zhang
RNA modifications have been proven to play fundamental roles in regulating cellular biology process. Recently, maladjusted N7-methylguanosine (m7G) modification and its modifiers METTL1/WDR4 have been confirmed an oncogene role in multiple cancers. However, the functions and molecular mechanisms of METTL1/WDR4 in acute myeloid leukemia (AML) remain to be determined. METTL1/WDR4 expression levels were
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Correction: Breast cancer heterogeneity and its implication in personalized precision therapy Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-23 Liantao Guo, Deguang Kong, Jianhua Liu, Ling Zhan, Lan Luo, Weijie Zheng, Qingyuan Zheng, Chuang Chen, Shengrong Sun
Correction: Experimental Hematology & Oncology (2023) 12:3 https://doi.org/10.1186/s40164-022-00363-1 In the Funding secion of this article [1], the grant number relating to National Natural Science Foundation of China was given incorrectly as No.8210114078 and should have been No.82103671. Funding This work was funded by the National Natural Science Foundation of China (Grant No.82103671). The original
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Crosstalk between colorectal CSCs and immune cells in tumorigenesis, and strategies for targeting colorectal CSCs Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-22 Qi Zhao, Hong Zong, Pingping Zhu, Chang Su, Wenxue Tang, Zhenzhen Chen, Shuiling Jin
Cancer immunotherapy has emerged as a promising strategy in the treatment of colorectal cancer, and relapse after tumor immunotherapy has attracted increasing attention. Cancer stem cells (CSCs), a small subset of tumor cells with self-renewal and differentiation capacities, are resistant to traditional therapies such as radiotherapy and chemotherapy. Recently, CSCs have been proven to be the cells
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ZMIZ2 facilitates hepatocellular carcinoma progression via LEF1 mediated activation of Wnt/β-catenin pathway Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-22 Yang Ding, Yumei Ning, Hui Kang, Yuan Yuan, Kun Lin, Chun Wang, Yun Yi, Jianghua He, Lurao Li, Xingxing He, Ying Chang
Hepatocellular carcinoma (HCC) is one of the most common malignancies with a high lethality rate. ZMIZ2 is a transcriptional co-activator implicated in various human diseases. However, the role and molecular mechanism of ZMIZ2 in HCC remains to be elucidated. The expression and prognostic value of ZMIZ2 in HCC was excavated from public databases and explored by bioinformatic analysis. Then the expression
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Outcomes of allogeneic hematopoietic stem cell transplantation in R/R DLBCL patients with failure of CAR-T therapy Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-16 Mengya Cong, Sicheng Ai, Liqing Kang, Mao Jin, Ying Zhu, Caixia Li, Zhengming Jin, Lei Yu, Depei Wu, Haiwen Huang
From October 2017 to June 2022, we retrospectively report outcomes of R/R DLBCL patients with failure of CAR-T therapy, then receiving allo-HSCT. Among 10 patients, 5 were males and 5 females, with a median age of 43.5 (27–52) years. All patients were diagnosed refractory/relapsed diffuse large B cell lymphoma. The median time from CAR-T treatment to transplantation was 84.5 (31–370) days. The median
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The roles of tissue resident macrophages in health and cancer Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-16 Minmin Cao, Zihao Wang, Wanying Lan, Binghua Xiang, Wenjun Liao, Jie Zhou, Xiaomeng Liu, Yiling Wang, Shichuan Zhang, Shun Lu, Jinyi Lang, Yue Zhao
As integral components of the immune microenvironment, tissue resident macrophages (TRMs) represent a self-renewing and long-lived cell population that plays crucial roles in maintaining homeostasis, promoting tissue remodeling after damage, defending against inflammation and even orchestrating cancer progression. However, the exact functions and roles of TRMs in cancer are not yet well understood
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Molecular profiling of biliary tract cancers reveals distinct genomic landscapes between circulating and tissue tumor DNA Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-08 Clémence Astier, Carine Ngo, Léo Colmet-Daage, Virginie Marty, Olivia Bawa, Claudio Nicotra, Maud Ngo-Camus, Antoine Italiano, Christophe Massard, Jean-Yves Scoazec, Cristina Smolenschi, Michel Ducreux, Antoine Hollebecque, Sophie Postel-Vinay
Biliary tract cancers (BTCs) are heterogeneous malignancies with dismal prognosis due to tumor aggressiveness and poor response to limited current therapeutic options. Tumor exome profiling has allowed to successfully establish targeted therapeutic strategies in the clinical management of cholangiocarcinoma (CCA). Still, whether liquid biopsy profiling could inform on BTC biology and patient management
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Recent updates on central nervous system prophylaxis in patients with high-risk diffuse large B-cell lymphoma Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2024-01-03 Bernard Ji Guang Chua, Chen Ee Low, Chun En Yau, Ya Hwee Tan, Jianbang Chiang, Esther Wei Yin Chang, Jason Yongsheng Chan, Eileen Yi Ling Poon, Nagavalli Somasundaram, Mohamed Farid Bin Harunal Rashid, Miriam Tao, Soon Thye Lim, Valerie Shiwen Yang
The use of central nervous system (CNS) prophylaxis for patients with diffuse large B-cell lymphoma (DLBCL) remains controversial. Although uncommon, CNS relapses are invariably fatal in this otherwise curable disease. Accurate identification of patients at risk and the optimal approach to CNS prophylaxis therefore remains an area of unmet need. The existing literature, largely retrospective in nature
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Targeting ST8SIA6-AS1 counteracts KRASG12C inhibitor resistance through abolishing the reciprocal activation of PLK1/c-Myc signaling Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-12-16 Yafang Wang, Mingyue Yao, Cheng Li, Kexin Yang, Xiaolong Qin, Lansong Xu, Shangxuan Shi, Chengcheng Yu, Xiangjun Meng, Chengying Xie
KRASG12C inhibitors (KRASG12Ci) AMG510 and MRTX849 have shown promising efficacy in clinical trials and been approved for the treatment of KRASG12C-mutant cancers. However, the emergence of therapy-related drug resistance limits their long-term potential. This study aimed to identify the critical mediators and develop overcoming strategies. By using RNA sequencing, RT-qPCR and immunoblotting, we identified
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ProNGF promotes brain metastasis through TrkA/EphA2 induced Src activation in triple negative breast cancer cells Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-12-10 Julien Cicero, Sarah Trouvilliez, Martine Palma, Gaetan Ternier, Laurine Decoster, Eloise Happernegg, Nicolas Barois, Alexandre Van Outryve, Lucie Dehouck, Roland P. Bourette, Eric Adriaenssens, Chann Lagadec, Cagatay Mehmet Tarhan, Dominique Collard, Zied Souguir, Elodie Vandenhaute, Grégory Maubon, François Sipieter, Nicolas Borghi, Fumitaka Shimizu, Takashi Kanda, Paolo Giacobini, Fabien Gosselet
Triple-Negative Breast Cancer is particularly aggressive, and its metastasis to the brain has a significant psychological impact on patients' quality of life, in addition to reducing survival. The development of brain metastases is particularly harmful in triple-negative breast cancer (TNBC). To date, the mechanisms that induce brain metastasis in TNBC are poorly understood. Using a human blood–brain
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The role of pyroptosis and gasdermin family in tumor progression and immune microenvironment Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-12-08 Mengyuan Li, Ping Jiang, Yuhan Yang, Liting Xiong, Shuhua Wei, Junjie Wang, Chunxiao Li
Pyroptosis, an inflammatory programmed cell death, distinguishes itself from apoptosis and necroptosis and has drawn increasing attention. Recent studies have revealed a correlation between the expression levels of many pyroptosis-related genes and both tumorigenesis and progression. Despite advancements in cancer treatments such as surgery, radiotherapy, chemotherapy, and immunotherapy, the persistent
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Antitumor effect of a small-molecule inhibitor of KRASG12D in xenograft models of mucinous appendicular neoplasms Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-12-08 Mari C. Vázquez-Borrego, Melissa Granados-Rodríguez, Florina I. Bura, Ana Martínez-López, Blanca Rufián-Andújar, Francisca Valenzuela-Molina, Lidia Rodríguez-Ortiz, Sergio Haro-Yuste, Ana Moreno-Serrano, Rosa Ortega-Salas, Rafael Pineda-Reyes, Carmen Michán, José Alhama, Antonio Romero-Ruiz, Álvaro Arjona-Sánchez
Pseudomyxoma peritonei (PMP) is a rare disease characterized by a massive accumulation of mucus in the peritoneal cavity. The only effective treatment is aggressive surgery, aimed at removing all visible tumors. However, a high percentage of patients relapse, with subsequent progression and death. Recently, there has been an increase in therapies that target mutated oncogenic proteins. In this sense
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A bile-based microRNA signature for differentiating malignant from benign pancreaticobiliary disease Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-12-01 Mireia Mato Prado, Jisce R. Puik, Leandro Castellano, Elena López-Jiménez, Daniel S. K. Liu, Laura L. Meijer, Tessa Y. S. Le Large, Eleanor Rees, Niccola Funel, Shivan Sivakumar, Stephen P. Pereira, Geert Kazemier, Babs M. Zonderhuis, Joris I. Erdmann, Rutger-Jan Swijnenburg, Andrea Frilling, Long R. Jiao, Justin Stebbing, Elisa Giovannetti, Jonathan Krell, Adam E. Frampton
Differentiating between pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA) is crucial for the appropriate course of treatment, especially with advancements in the role of neoadjuvant chemotherapies for PDAC, compared to CCA. Furthermore, benign pancreaticobiliary diseases can mimic malignant disease, and indeterminate lesions may require repeated investigations to achieve a diagnosis
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Upregulated PARP1 confers breast cancer resistance to CDK4/6 inhibitors via YB-1 phosphorylation Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-11-30 Chuntao Quan, Zhijie Wu, Juan Xiong, Manqing Li, Yu Fu, Jiaying Su, Yue Wang, Lvwen Ning, Deju Zhang, Ni Xie
Cyclic-dependent kinase (CDK) 4/6 kinases, as the critical drivers of the cell cycle, are involved in the tumor progression of various malignancies. Pharmacologic inhibitors of CDK4/6 have shown significant clinical prospects in treating hormone receptor-positive and human epidermal growth factor receptor-negative (HR + /HER2-) breast cancer (BC) patients. However, acquired resistance to CDK4/6 inhibitors
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Immune checkpoint inhibitors for multiple myeloma immunotherapy Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-11-28 Zhaoyun Liu, Xintong Xu, Hui Liu, Xianghong Zhao, Chun Yang, Rong Fu
Multiple myeloma (MM) is related to immune disorders, recent studys have revealed that immunotherapy can greatly benefit MM patients. Immune checkpoints can negatively modulate the immune system and are closely associated with immune escape. Immune checkpoint-related therapy has attracted much attention and research in MM. However, the efficacy of those therapies need further improvements. There need
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Single VHH-directed BCMA CAR-NK cells for multiple myeloma Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-11-27 Quan Ren, Yingling Zu, Hongchang Su, Qiumei Lu, Bin Xiang, Yanping Luo, Jishuai Zhang, Yongping Song
Natural killer (NK) cells are promising alternatives for the production of “off-the-shelf” CAR products, posing a lower risk of cytokine release syndrome (CRS) than CAR-T cells. We synthesized four single VHH-directed anti-BCMA CARs, incorporating various intracellular regions (2B4 versus CD28) and hinge domains (CD28 versus IgG1) and ectopically producing IL-15. NK cells derived from peripheral blood
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Deciphering tumor-infiltrating dendritic cells in the single-cell era Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-11-27 Qingyu Huang, Fuhao Wang, Di Hao, Xinyu Li, Xiaohui Li, Tianyu Lei, Jinbo Yue, Chao Liu
Dendritic cells (DCs) serve as a pivotal link connecting innate and adaptive immunity by processing tumor-derived antigens and activating T cells. The advent of single-cell sequencing has revolutionized the categorization of DCs, enabling a high-resolution characterization of the previously unrecognized diversity of DC populations infiltrating the intricate tumor microenvironment (TME). The application
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Molecular characterization of the CXCR4 / CXCR7 axis in germ cell tumors and its targetability using nanobody-drug-conjugates Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-11-23 Gamal A. Wakileh, Philipp Bierholz, Mara Kotthoff, Margaretha A. Skowron, Felix Bremmer, Alexa Stephan, Stephanie M. Anbuhl, Raimond Heukers, Martine J. Smit, Philipp Ströbel, Daniel Nettersheim
Being stimulated by the chemokine CXCL12, the CXCR4 / CXCR7 cascade is involved in tumor proliferation, migration, and metastasis. The interaction between CXCL12, secreted by cells from the microenvironment, and its receptors is complex and has been ascribed to promote chemotherapy resistance. However, the role of this signaling axis and its targetability in germ cell tumors (GCT) is not fully understood
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CRISPR/Cas9 system: recent applications in immuno-oncology and cancer immunotherapy Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-11-14 Chen Chen, Zehua Wang, Yanru Qin
Clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is essentially an adaptive immunity weapon in prokaryotes against foreign DNA. This system inspires the development of genome-editing technology in eukaryotes. In biomedicine research, CRISPR has offered a powerful platform to establish tumor-bearing models and screen potential targets in the immuno-oncology
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Downregulation of pro-surfactant protein B contributes to the recurrence of early-stage non-small cell lung cancer by activating PGK1-mediated Akt signaling Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-11-09 Hao Luo, Qing Li, Ren-Tao Wang, Liang Zhang, Wei Zhang, Meng-Sheng Deng, Yuan-Yuan Luo, Xintong Ji, Yongheng Wen, Xuan-Rui Zhou, Bo Xu, Dong Wang, Bin Hu, Hua Jin, Cheng-Xiong Xu
Recurrence is one of the main causes of treatment failure in early-stage non-small cell lung cancer (NSCLC). However, there are no predictors of the recurrence of early-stage NSCLC, and the molecular mechanism of its recurrence is not clear. In this study, we used clinical sample analysis to demonstrate that low levels of expression of precursor surfactant protein B (pro-SFTPB) in primary NSCLC tissue
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The current landscape of using direct inhibitors to target KRASG12C-mutated NSCLC Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-11-04 Firas Batrash, Mahmoud Kutmah, Jun Zhang
Mutation in KRAS protooncogene represents one of the most common genetic alterations in NSCLC and has posed a great therapeutic challenge over the past ~ 40 years since its discovery. However, the pioneer work from Shokat’s lab in 2013 has led to a recent wave of direct KRASG12C inhibitors that utilize the switch II pocket identified. Notably, two of the inhibitors have recently received US FDA approval
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Chinese expert consensus on Bruton tyrosine kinase inhibitors in the treatment of B-cell malignancies Exp. Hematol. Oncol. (IF 10.9) Pub Date : 2023-10-16 Yuqin Song, Shang-Ju Wu, Zhixiang Shen, Donglu Zhao, Thomas Sau Yan Chan, Huiqiang Huang, Lugui Qiu, Jianyong Li, Tran-der Tan, Jun Zhu, Yongping Song, Wei-Han Huang, Weili Zhao, Herman Sung Yu Liu, Wei Xu, Naizhi Chen, Jun Ma, Cheng-Shyong Chang, Eric Wai Choi Tse
Targeted therapy with Bruton tyrosine kinase (BTK) inhibitors have revolutionized the treatment of patients with various B-cell malignancies. BTK inhibitors such as ibrutinib, zanubrutinib, orelabrutinib, and acalabrutinib have shown good clinical efficacy and better safety profiles than those of traditional chemotherapy and chemoimmunotherapy regimens. Multiple studies on new BTK inhibitors are ongoing