Abstract
It is important to evaluate the clinical importance of both CD8 T cells and CD4 T cells expression simultaneously because they have crucial networks in tumour targeting immune responses. In 97 RCC patients, RNA sequencing and gene set enrichment analysis of both CD8 and CD4 T cells based on the expression levels of PD-1 and TIM-3 implied that the populations of PD-1+TIM-3+ CD8 T cells and PD-1lowTIM-3 + CD4 T cells were characterized as exhausted CD8 T cells and regulatory CD4 T cells, respectively. These populations of CD4 and CD8 T cells were significantly upregulated in the patients with RCC of higher WHO/ISUP grade (grades 3, 4) (P < 0.001). Moreover, the cytokine productivities of each population in both CD4 and CD8 T cells of the higher-grade patients were significantly lower than those of the lower-grade patients (P < 0.05). Multivariate analysis showed the prognosis of patients with metastatic RCC of higher WHO/ISUP grade treated by nivolumab to be significantly worse than that of patients with lower grade (P = 0.026). This study showed that tumour grade significantly correlated with dysfunction of both CD4+ and CD8+ TILs and the efficacy of nivolumab treatment.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Antineoplastic Agents, Immunological / pharmacology
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Antineoplastic Agents, Immunological / therapeutic use
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Carcinoma, Renal Cell / diagnosis*
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Carcinoma, Renal Cell / drug therapy
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Carcinoma, Renal Cell / immunology
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Carcinoma, Renal Cell / mortality
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Cytokines / metabolism
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Female
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Follow-Up Studies
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Hepatitis A Virus Cellular Receptor 2 / metabolism
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Humans
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Kidney / pathology
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Kidney Neoplasms / diagnosis*
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Kidney Neoplasms / drug therapy
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Kidney Neoplasms / immunology
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Kidney Neoplasms / mortality
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Lymphocytes, Tumor-Infiltrating / immunology*
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Lymphocytes, Tumor-Infiltrating / metabolism
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Male
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Middle Aged
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Neoplasm Grading
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Nivolumab / pharmacology
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Nivolumab / therapeutic use
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Prognosis
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Programmed Cell Death 1 Receptor / antagonists & inhibitors
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Programmed Cell Death 1 Receptor / metabolism
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Progression-Free Survival
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RNA-Seq
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Retrospective Studies
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism
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Treatment Outcome
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Tumor Microenvironment / drug effects
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Tumor Microenvironment / immunology*
Substances
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Antineoplastic Agents, Immunological
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Cytokines
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HAVCR2 protein, human
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Hepatitis A Virus Cellular Receptor 2
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PDCD1 protein, human
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Programmed Cell Death 1 Receptor
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Nivolumab