TOX-expressing terminally exhausted tumor-infiltrating CD8 + T cells are reinvigorated by co-blockade of PD-1 and TIGIT in bladder cancer.

Autor: Han HS; Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Republic of Korea; Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea., Jeong S; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea., Kim H; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea., Kim HD; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea., Kim AR; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea., Kwon M; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea., Park SH; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea., Woo CG; Department of Pathology, Chungbuk National University Hospital, Cheongju, Republic of Korea., Kim HK; Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea., Lee KH; Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Republic of Korea; Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea., Seo SP; Department of Urology, Chungbuk National University Hospital, Cheongju, Republic of Korea., Kang HW; Department of Urology, Chungbuk National University Hospital, Cheongju, Republic of Korea; Department of Urology, Chungbuk National University College of Medicine, Cheongju, Republic of Korea., Kim WT; Department of Urology, Chungbuk National University Hospital, Cheongju, Republic of Korea; Department of Urology, Chungbuk National University College of Medicine, Cheongju, Republic of Korea., Kim WJ; Department of Urology, Chungbuk National University Hospital, Cheongju, Republic of Korea; Department of Urology, Chungbuk National University College of Medicine, Cheongju, Republic of Korea., Yun SJ; Department of Urology, Chungbuk National University Hospital, Cheongju, Republic of Korea; Department of Urology, Chungbuk National University College of Medicine, Cheongju, Republic of Korea. Electronic address: sjyun@chungbuk.ac.kr., Shin EC; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. Electronic address: euicheols@kaist.ac.kr.
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2021 Feb 28; Vol. 499, pp. 137-147. Date of Electronic Publication: 2020 Nov 27.
DOI: 10.1016/j.canlet.2020.11.035
Abstrakt: Exhausted T cells in the tumor microenvironment are major targets of immunotherapies. However, the exhaustion status of CD8 + tumor-infiltrating lymphocytes (TILs) in bladder cancer has not been comprehensively evaluated. Herein, we examined distinct exhaustion status of CD8 + TILs based on the level of programmed cell death-1 (PD-1) and thymocyte selection-associated high mobility group box protein (TOX) expression in urothelial bladder cancer. We also evaluated the reinvigoration of exhausted CD8 + TILs upon ex vivo treatment with inhibitory checkpoint blockers. TOX-expressing PD-1 high CD8 + TILs had the highest expression of immune checkpoint receptors (ICRs), the most terminally exhausted features, and the highest tumor antigen reactivity among PD-1 + CD8 + TILs. Bladder cancer patients with a high percentage of PD-1 high TOX + CD8 + TILs had more progressed T-cell exhaustion features and higher programmed death-ligand 1 expression in tumor tissues. TIGIT was the most frequent co-expressed ICR on PD-1 + CD8 + TILs, and TIGIT blockade enhanced the PD-1 blockade-mediated cytokine production by CD8 + TILs from bladder cancer patients. Our findings provide an improved understanding of the heterogeneous exhaustion status of CD8 + TILs and additional immunotherapy strategies to improve outcomes of bladder cancer patients.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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