Clonal hematopoiesis (CH), an expansion of hematopoietic clones harboring somatic mutations, is common in patients with solid tumors and associates with poor outcomes. In this issue of Cancer Cell, a study shows that, in response to immunotherapy, TET2-mutant CH enhances macrophage antigen presentation and CD8⁺ T cell activation, thereby improving therapeutic efficacy.

Immunotherapy reshapes the interaction between the tumor microenvironment and cancer stem cells. In this issue of Cancer Cell, Guo et al. revealed that SOX2High tumor-initiating stem cells reprogram neutrophils that block interferon-induced reprogramming after immunotherapy, maintaining their pro-tumor phenotype at the tumor-stroma interface.

Glioblastoma features extensive gene expression heterogeneity and high lethality, yet the mechanisms underlying this heterogeneity and its link to clinical outcomes remain elusive. In this issue of Cancer Cell, Migliozzi et al. spatially profile glioblastoma specimens to uncover cellular mechanisms that govern the extent of the heterogeneity in malignant cells.

Extrachromosomal circular DNA (ecDNA), enriched with enhancers, drives oncogenic transcription and tumor progression, but the mechanisms remain elusive. In this issue of Cancer Cell, Wei et al. uncover MED1-driven ecDNA super-enhancers as regulatory hubs and show that disrupting ecDNA-containing condensates selectively impairs transcription and induces apoptosis in a cancer-type-specific manner.

Exercise holds significant potential as an adjunct therapy in cancer, extending beyond quality-of-life improvements to influencing tumor progression, treatment response, and survival. Its clinical integration remains limited by variability in models, heterogenous interventions, and the absence of predictive biomarkers. As the field progresses, identifying molecular effectors of exercise, in addition

The spatial landscape of the tumor immune microenvironment (TIME) is under significant investigation as a driver of immunotherapy resistance in solid tumors. Most work centers on constituent immune cells within intra-tumoral niches, overlooking tumor cell phenotypes. Yet cancer cells shape their milieu by multiple modalities, including secreting and depleting metabolites. Here, we argue that integrating

For resectable pancreatic cancer, upfront surgery followed by adjuvant therapy has long been the standard of care. A randomized trial by Bai et al. in Cancer Cell demonstrates that sequential neoadjuvant gemcitabine/nab-paclitaxel followed by mFOLFIRINOX significantly improved event-free survival compared with upfront surgery, supporting a shift toward a sequential neoadjuvant approach in this setting

Cellular senescence plays dual roles in precancer lesions: initially serving as a tumor-suppressive barrier within the epithelial compartment and later contributing to a pro-tumoral precancer tissue microenvironment (PreTME) via a sustained, paracrine secretome known as senescent-associated secretory phenotype (SASP). This commentary highlights the role of senescence across various PreTME cell types

In this issue of Cancer Cell, Galeano Niño et al. report that tumor-infiltrating bacteria like Fusobacterium species induce a quiescent, chemoresistant state in cancer cells in the colon by disrupting epithelial contacts and suppressing proliferation and transcription. These studies highlight microbial-tumor interactions as potential modulators of therapeutic response in colon cancer.

(Cancer Cell 36, 139–155.e1–e10, August 12, 2019)

Allogeneic natural killer (NK) cell immunotherapy is emerging as a promising and scalable, off-the-shelf platform for treating relapsed and refractory cancers. Early-phase clinical trials have demonstrated remarkable safety and encouraging therapeutic efficacy of chimeric antigen receptor (CAR)-NK cells in heavily pretreated patients with lymphoid malignancies. Current efforts are expanding these therapies

Immunotherapy as single-agent PD-1 blockade does not work for patients with microsatellite stable (MSS) colorectal cancer. In this issue of Cancer Cell, Morris et al. demonstrate that targeting the mitogen-activated protein kinase (MAPK) pathway in combination with immunotherapy can reprogram BRAF-V600E mutant MSS colorectal cancers toward immune responsiveness.

Upfront resection is the standard treatment for localized dMMR/MSI-high colon cancer. In this issue of Cancer Cell, Wang et al. showed that dual anti-CTLA-4/PD-1 IBI310/sintilimab for 6 weeks improved pathological complete response over sintilimab in patients with cT4/N+ tumors. This combination represents a referral regimen for neoadjuvant or organ-preserving strategies.

The analysis of cell-free DNA (cfDNA) fragmentation patterns, known as “fragmentomics,” has opened new opportunities in noninvasive cancer diagnostics. Due to its close relationships with genomic organization and cell death, cfDNA fragmentomics lies at the intersection of many aspects of cancer biology, including epigenetic dysregulation, transcriptomic alterations, and aberrant cellular turnover patterns

(Cancer Cell 16, 295–308; October 6, 2009)

Harnessing the cytotoxic potential of natural killer (NK) cells for cancer immunotherapy has proven challenging. In this issue of Cancer Cell, Biederstädt et al. and Nikolic et al. utilize genome-wide CRISPR screening to uncover novel regulators of NK cell function, paving the way for developing next-generation NK cell therapies.

We propose an emerging strategy for advanced cancer treatment based on progressive, stepwise remodeling of tumor microenvironments (TMEs). TMEs are variable but show conserved archetypes across patients and tissue origins. Deep learning over single-cell atlases collected from perturbed tumors can uncover gene and cellular networks shifting between archetypes. This allows for designing “nudge” or “state-shifting”

(Cancer Cell 26, 707–721; November 10, 2014)

Glioblastoma alters normal brain function by hijacking neural circuits. In this issue of Cancer Cell, Yang et al. elucidate the mechanisms by which glioblastoma exploits cholinergic signaling pathways to disrupt the hierarchical organization of brain networks. These insights help redefine tumor-brain interactions and open new therapeutic avenues.

Treatment resistance limits long-term effectiveness in cancer therapy. Conventional biomarkers typically rely on static gene expression levels. In this issue of Cancer Cell, Jassim et al. report a new approach, RECODR, which captures how gene relationships shift over time, uncovering hidden drivers of resistance and suggesting effective combination treatments.

B cell lymphomas arise from mutations that disrupt normal germinal center B cell programs and promote a microenvironment that fosters aberrant proliferation and immune escape. In this issue of Cancer Cell, Hesterberg et al. show that lymphoma accelerates T cell aging by transcriptional and epigenetic reprogramming that mirrors physiological aging.

In this issue of Cancer Cell, Chen et al. identify DNASE1L3-expressing dendritic cells (DCs) as enhancers of anti-tumor immunity. By degrading neutrophil extracellular traps, these DCs promote CD8⁺ T cell infiltration into tumors and enhance checkpoint blockade efficacy, extending DNASE1L3’s known immune regulatory role to physical remodeling of the tumor microenvironment.

Cancer pain is a complex problem that, when left unaddressed, can impact overall survival and decrease patients’ quality of life. Collaboration among medical oncologists, immunologists, and neurobiologists in the cancer neuroscience field has recently revealed a pivotal role for the sensory nervous system in cancer progression. We highlight recent scientific findings suggesting that selection of appropriate

Follicular lymphoma is a neoplastic disease of B cell-rich follicular structures of lymphoid origin. In this issue of Cancer Cell, Abe et al. use multi-omics analyses to identify and characterize distinct follicular T cell subsets that can be used to stratify follicular lymphoma prognoses.

Circulating tumor cells (CTCs) are cancer cells, shed from primary tumors or metastases into the bloodstream. The first non-invasive “liquid biopsy” for cancer monitoring, CTCs have been largely surpassed by circulating tumor DNA (ctDNA) for clinical applications, given the ease of DNA sequencing without specialized cell isolation methods. However, emerging rare cell capture technologies that can process

Despite current progress, many patients with ovarian cancer (OC) often relapse after therapy. In this issue of Cancer Cell, Ghisoni et al. integrate multiomic and functional analyses to provide a roadmap for biomarker-driven therapy in OC and suggest that immune phenotyping could be incorporated into clinical stratification.

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