期刊
LIVER INTERNATIONAL
卷 41, 期 4, 页码 764-776出版社
WILEY
DOI: 10.1111/liv.14814
关键词
cholangiocarcinoma; immune checkpoint inhibitor; tissue‐ resident memory T cells; tumour‐ infiltrating lymphocytes
资金
- National Research Foundation of Korea (NRF)
- Korean government (MSIT) [NRF-2019R1A2C2005176]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI15C2859]
- Young Medical Scientist Research Grant through the Daewoong Foundation [DF-201906-0000003]
- Bio and Medical Technology Development Program from the National Research Foundation (NRF) - Korean Ministry of Science, Communications Technology, and Future Planning (MSIP) [NRF-2016M3A9E8941331]
The study investigated the implications of TRM-related features of tumour-infiltrating CD8(+) T cells in ICC patients, revealing that CD69(+)CD103(+) cells exhibited a stronger response to immune checkpoint inhibitors, while CD69(-) and CD69(+)CD103(-) cells were associated with the Wnt/β-catenin and TGF-beta pathways.
Background The heterogeneous immune landscapes of intrahepatic cholangiocarcinoma (ICC) remain largely unknown. Here we aimed to investigate the implications of tissue-resident memory (TRM)-related features of tumour-infiltrating CD8(+) T cells (CD8(+) TILs) from ICC patients. Methods From ICC patients, we obtained blood samples and ICC surgical specimens (n = 33). We performed multicolour flow cytometry, multiplexed immunohistochemistry and RNA sequencing. Results When compared to peripheral CD8(+) T cells, the CD8(+) TILs included significantly higher proportions of the CD69(+)CD103(-) and CD69(+)CD103(+) TRM-like subsets (P < .001 for both). Relative to CD69(-) and CD69(+)CD103(-) cells, the CD69(+)CD103(+) CD8(+) TILs harboured higher levels of T-cell markers representing tumour specificity (ie CD39), proliferation (ie Ki-67) and T-cell activation (ie HLA-DR and CD38) (all P < .001). Moreover, compared to the stroma, the tumour margin and core density each had a significantly higher density of CD103(+) CD8(+) TILs (P < .001 for both). ICCs with high proportions of CD69(+)CD103(+) cells displayed higher levels of parameters associated with response to immune checkpoint inhibitors (ICIs)-including number of CD8(+) TIL infiltrates (P = .019), PD-L1 expression in the tumour (P = .046) and expression of the T cell-inflamed gene signature (P < .001). ICCs with lower proportions of CD69(+)CD103(+) CD8(+) TILs exhibited significant enrichment of genes related to the Wnt/beta-catenin (P < .001) and TGF-beta pathways (P = .002). Conclusion CD69(+)CD103(+) TRM-like CD8(+) TILs represent prominent tumour-specific immune responses and hold promise as a potential therapeutic target in ICC patients. Differential TRM-related features of ICCs may help develop future immunotherapeutic strategies such as maximizing TRM responses or inhibiting pathways contributing to immune evasion.
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