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Non-terminally exhausted tumor-resident memory HBV-specific T cell responses correlate with relapse-free survival in hepatocellular carcinoma
Immunity ( IF 32.4 ) Pub Date : 2021-07-15 , DOI: 10.1016/j.immuni.2021.06.013
Yang Cheng 1 , Bavani Gunasegaran 1 , Harsimran D Singh 1 , Charles-Antoine Dutertre 2 , Chiew Yee Loh 1 , Jia Qi Lim 3 , Jeremy Chase Crawford 4 , Hong Kai Lee 1 , Xiaomeng Zhang 1 , Bernett Lee 1 , Etienne Becht 5 , Wan Jun Lim 6 , Joe Yeong 7 , Chung Yip Chan 8 , Alexander Chung 8 , Brian K P Goh 8 , Pierce K H Chow 9 , Jerry K Y Chan 10 , Florent Ginhoux 1 , David Tai 11 , Jinmiao Chen 1 , Seng Gee Lim 12 , Weiwei Zhai 13 , Su Pin Choo 6 , Evan W Newell 5
Affiliation  

Hepatocellular carcinoma (HCC) often develops following chronic hepatitis B virus (HBV) infection and responds poorly to immune checkpoint blockade. Here, we examined the antigen specificities of HCC-infiltrating T cells and their relevance to tumor control. Using highly multiplexed peptide-MHC tetramer staining of unexpanded cells from blood, liver, and tumor tissues from 46 HCC patients, we detected 91 different antigen-specific CD8+ T cell populations targeting HBV, neoantigen, tumor-associated, and disease-unrelated antigens. Parallel high-dimensional analysis delineated five distinct antigen-specific tissue-resident memory T (Trm) cell populations. Intratumoral and intrahepatic HBV-specific T cells were enriched for two Trm cell subsets that were PD-1loTOXlo, despite being clonally expanded. High frequencies of intratumoral terminally exhausted T cells were uncommon. Patients with tumor-infiltrating HBV-specific CD8+ Trm cells exhibited longer-term relapse-free survival. Thus, non-terminally exhausted HBV-specific CD8+ Trm cells show hallmarks of active involvement and effective antitumor response, implying that these cells could be harnessed for therapeutic purposes.



中文翻译:

非终末耗尽的肿瘤驻留记忆 HBV 特异性 T 细胞反应与肝细胞癌的无复发生存相关

肝细胞癌 (HCC) 通常在慢性乙型肝炎病毒 (HBV) 感染后发生,并且对免疫检查点封锁反应不佳。在这里,我们检查了 HCC 浸润性 T 细胞的抗原特异性及其与肿瘤控制的相关性。使用来自 46 名 HCC 患者的血液、肝脏和肿瘤组织的未扩增细胞的高度多重肽-MHC 四聚体染色,我们检测到 91 种不同的抗原特异性 CD8 + T 细胞群,针对 HBV、新抗原、肿瘤相关和疾病无关抗原. 平行高维分析描绘了五种不同的抗原特异性组织驻留记忆 T (Trm) 细胞群。肿瘤内和肝内 HBV 特异性 T 细胞富集了两个 Trm 细胞亚群,它们是 PD-1 lo TOX lo,尽管被克隆扩展。肿瘤内终末耗竭的高频率 T 细胞并不常见。具有肿瘤浸润性 HBV 特异性 CD8 + Trm 细胞的患者表现出长期无复发存活率。因此,非终末耗尽的 HBV 特异性 CD8 + Trm 细胞显示出积极参与和有效抗肿瘤反应的标志,这意味着这些细胞可以用于治疗目的。

更新日期:2021-08-10
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