新加坡A*STAR研究所Evan W. Newell团队发现，非终末耗竭的肿瘤驻留记忆性HBV特异性T细胞反应与肝细胞癌的无复发生存期有关。该项研究成果于2021年7月15日在线发表在《免疫》杂志上。

研究人员揭示了肝细胞癌（HCC）浸润性T细胞的抗原特异性及其与肿瘤控制的相关性。通过对46名HCC患者的血液、肝脏和肿瘤组织中未扩增的细胞进行高度复用的肽-MHC四聚体染色，研究人员检测到91种不同的抗原特异性CD8⁺T细胞群，这些细胞群以乙型肝炎病毒（HBV）、新抗原、肿瘤相关和疾病无关的抗原为靶标。平行的高维分析划定了五个不同的抗原特异性组织驻留记忆T（Trm）细胞群。瘤内和肝内HBV特异性T细胞富集了两个Trm细胞亚群，尽管出现克隆扩增，这两个亚群均是PD-1^loTOX^lo。

高频率的瘤内终末衰竭T细胞并不常见。具有肿瘤浸润性HBV特异性CD8⁺Trm细胞的患者表现出较长的无复发生存期。因此，非终末衰竭的HBV特异性CD8⁺Trm细胞显示出主动参与和有效抗肿瘤反应的特征，这意味着这些细胞可以被用于治疗。

据悉，HCC经常在慢性HBV感染后发病，对免疫检查点阻断的反应很差。

附：英文原文

Title: Non-terminally exhausted tumor-resident memory HBV-specific T cell responses correlate with relapse-free survival in hepatocellular carcinoma

Author: Yang Cheng, Bavani Gunasegaran, Harsimran D. Singh, Charles-Antoine Dutertre, Chiew Yee Loh, Jia Qi Lim, Jeremy Chase Crawford, Hong Kai Lee, Xiaomeng Zhang, Bernett Lee, Etienne Becht, Wan Jun Lim, Joe Yeong, Chung Yip Chan, Alexander Chung, Brian K.P. Goh, Pierce K.H. Chow, Jerry K.Y. Chan, Florent Ginhoux, David Tai, Jinmiao Chen, Seng Gee Lim, Weiwei Zhai, Su Pin Choo, Evan W. Newell

Issue&Volume: 2021-07-15

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

DOI: 10.1016/j.immuni.2021.06.013

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00257-0