Multifunctionality of CD8 + T cells and PD‐L1 expression as a biomarker of anti‐PD‐1 antibody efficacy in advanced melanoma
| العنوان: | Multifunctionality of CD8 + T cells and PD‐L1 expression as a biomarker of anti‐PD‐1 antibody efficacy in advanced melanoma |
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| المؤلفون: | Heiichiro Udono, Osamu Yamasaki, Shin Morizane, Yuki Nakagawa, Keiko Manabe, Tomoko Miyake |
| المصدر: | The Journal of Dermatology. 48:1186-1192 |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Interleukin 2, business.industry, Melanoma, medicine.medical_treatment, Dermatology, General Medicine, medicine.disease, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Cytokine, Antigen, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, Medicine, Cytotoxic T cell, Nivolumab, business, CD8, medicine.drug |
| الوصف: | 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. |
| تدمد: | 1346-8138 0385-2407 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::c869c86ea85ee57bd7db4e7a0488d529 https://doi.org/10.1111/1346-8138.15904 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........c869c86ea85ee57bd7db4e7a0488d529 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13468138 03852407 |
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