التفاصيل البيبلوغرافية
| العنوان: |
Non-terminally exhausted tumor-resident memory HBV-specific T cell responses correlate with relapse-free survival in hepatocellular carcinoma. |
| المؤلفون: |
Cheng, Yang1 (AUTHOR), Gunasegaran, Bavani1 (AUTHOR), Singh, Harsimran D.1 (AUTHOR), Dutertre, Charles-Antoine1,2,3 (AUTHOR), Loh, Chiew Yee1 (AUTHOR), Lim, Jia Qi4 (AUTHOR), Crawford, Jeremy Chase5 (AUTHOR), Lee, Hong Kai1 (AUTHOR), Zhang, Xiaomeng1 (AUTHOR), Lee, Bernett1 (AUTHOR), Becht, Etienne1,6 (AUTHOR), Lim, Wan Jun7 (AUTHOR), Yeong, Joe1,8 (AUTHOR), Chan, Chung Yip9,10 (AUTHOR), Chung, Alexander9,10 (AUTHOR), Goh, Brian K.P.9,10 (AUTHOR), Chow, Pierce K.H.9,10,11 (AUTHOR), Chan, Jerry K.Y.12,13 (AUTHOR), Ginhoux, Florent1 (AUTHOR), Tai, David7,10 (AUTHOR) |
| المصدر: |
Immunity (10747613). Aug2021, Vol. 54 Issue 8, p1825-1825. 1p. |
| مصطلحات موضوعية: |
*T cells, *CHRONIC hepatitis B, *HEPATOCELLULAR carcinoma, *IMMUNE checkpoint proteins, *HEPATITIS B virus, *CELL populations, *AUTOBIOGRAPHICAL memory, *BLOOD cells |
| مستخلص: |
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-1lo TOX lo, 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. [Display omitted] • Broad analysis of CD8+ T cell antigen specificity in HBV-HCC patient blood, liver, tumor • Tumor-infiltrating HBV-specific T cells correlate with superior relapse-free survival • Five Trm subsets are enriched in liver- and tumor-infiltrating HBV-specific T cells • HBV-specific Trm cells have expanded TCR clones and lack hallmarks of terminal exhaustion Hepatocellular carcinoma (HCC) often develops following chronic hepatitis B virus (HBV) infection and responds poorly to immune checkpoint blockade. Cheng et al. examine the antigen specificities of HCC-infiltrating T cells and reveal that HBV-specific Trm cells are phenotypically distinct, clonally expanded, and are not terminally exhausted, suggesting that these cells may be harnessed for therapeutic purposes. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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