Implication of CD69(+)CD103(+) tissue-resident-like CD8(+) T cells as a potential immunotherapeutic target for cholangiocarcinoma
- Abstract
- 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.
- Author(s)
- 김상엽; 김형돈; 박성열; 박수형; 송기원; 신의철; 신재훈; 유창훈; 이단비; 이용준; 이재훈; 정성주; 주영석; 황신
- Issued Date
- 2021
- Type
- Article
- Keyword
- cholangiocarcinoma; immune checkpoint inhibitor; Immunohistochemistry; Immunotherapy; Memory; T cells; tissue‐resident memory T cells; tumour‐infiltrating lymphocytes
- DOI
- 10.1111/liv.14814
- URI
- https://oak.ulsan.ac.kr/handle/2021.oak/8531
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_proquest_miscellaneous_2487156132&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Implication%20of%20CD69(%2B)CD103(%2B)%20tissue-resident-like%20CD8(%2B)%20T%20cells%20as%20a%20potential%20immunotherapeutic%20target%20for%20cholangiocarcinoma&offset=0&pcAvailability=true
- Publisher
- LIVER INTERNATIONAL
- Location
- 미국
- Language
- 영어
- ISSN
- 1478-3223
- Citation Volume
- 41
- Citation Number
- 4
- Citation Start Page
- 764
- Citation End Page
- 776
-
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