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Multifunctionality of CD8 + T cells and PD‐L1 expression as a biomarker of anti‐PD‐1 antibody efficacy in advanced melanoma
Author(s) -
Manabe Keiko,
Yamasaki Osamu,
Nakagawa Yuki,
Miyake Tomoko,
Udono Heiichiro,
Morizane Shin
Publication year - 2021
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/1346-8138.15904
Subject(s) - nivolumab , cd8 , tumor infiltrating lymphocytes , medicine , melanoma , antibody , tumor necrosis factor alpha , immune system , cytokine , immunotherapy , pd l1 , immunology , antigen , cancer research , t cell
Anti‐programmed cell death protein‐1 (PD‐1) antibodies have become a standard treatment for advanced melanoma. However, a predictive biomarker for assessing the efficacy of anti‐PD‐1 antibodies has not been identified. In cancer, CD8 + T cells specific for tumor antigens undergo repeated T‐cell receptor stimulation due to the persistence of cancer cells and gradually lose their ability to secrete interleukin 2 (IL‐2), tumor necrosis factor‐α (TNF‐α), and interferon‐γ (IFN‐γ). We aimed to evaluate multi‐cytokine production and immune exhaustion of peripheral CD8 + T cells in melanoma patients treated with anti‐PD‐1 antibodies. Twenty‐four melanoma patients treated with nivolumab were included. Effector cytokine production (IL‐2, TNF‐α, and IFN‐γ) and expression of an exhaustion marker (PD‐1) in patients’ CD8 + cells were analyzed with flow cytometry. The relationships between parameters such as the neutrophil‐to‐lymphocyte ratio (NLR) and clinical response to nivolumab were examined. Immunohistochemistry for programmed death‐ligand 1 (PD‐L1) expression in tumor cells and tumor‐infiltrating lymphocytes (TILs) and analysis of their association with clinical response were performed. The clinical response rate to nivolumab was 29%. Regarding TILs, NLR, and several other parameters, no significant difference was found between responders and non‐responders. The responder group showed an increase in the percentage of PD‐1 + CD8 + /TNF‐α + IFN‐γ + or PD‐1 + CD8 + /IFN‐γ + IL‐2 + TNF‐α + T cells compared to non‐responders. Positivity for PD‐L1 expression was significantly higher in the responder group than the non‐responder group. In advanced melanoma, the percentage of multifunctional CD8 + PD‐1 + T cells and PD‐L1 expression in the tumors may be a biomarker for a good response to anti‐PD‐1 antibody monotherapy.