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Updated: Apr 5, 2026
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Tim-3 expression represents dysfunctional tumor infiltrating T cells in renal cell carcinoma
Chen Cai1, Yi-Fan Xu2, Zhen-Jie Wu3
1Department of Special Clinic, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
Purpose:
Renal cell carcinoma (RCC) is the most common cancer of kidney. Evidences have shown that RCC is sensitive to various immunotherapies. Tim-3 plays a role in suppressing Th1-mediated immune responses. However, no study has yet examined the effect of Tim-3 on tumor infiltrating lymphocytes (TILs) in RCC.
Methods:
We investigated the expression and function of Tim-3 on TIL CD4+ T cells and TIL CD8+ T cells from 30 RCC patients.
Results:
Levels of Tim-3 were significantly increased on both TIL CD4+ T cells and TIL CD8+ T cells and were associated with higher stages of the cancer. Also, GATA-3 and interferon gamma (IFN-γ) were down-regulated, whereas T-bet was up-regulated in TIL Tim-3+ T cells, indicating that Tim-3 expression defined a population of dysfunctional TIL Th1/Tc1 cells. Mechanism analyses showed that TIL Tim-3-expressing CD8+ T cells exhibited impaired Stat5 and p38 signaling pathway. Blocking the Tim-3 pathway restored cell proliferation and increased IFN-γ production in TIL CD4+ and CD8+ T cells of RCC.
Conclusions:
These results suggest that Tim-3 may be used as a novel target for increasing immune responses in RCC tumor microenvironment.
Insights
Tim-3 is elevated in renal cell carcinoma (RCC) and impairs tumor-infiltrating lymphocytes (TILs). Blocking Tim-3 enhances anti-tumor immune responses in RCC, suggesting it as a potential therapeutic target.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Renal cell carcinoma (RCC) is the most common kidney cancer and shows sensitivity to immunotherapy.
- T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) is known to suppress Th1-mediated immune responses.
- The role of Tim-3 in tumor-infiltrating lymphocytes (TILs) within the RCC microenvironment remains unexplored.
Purpose of the Study:
- To investigate the expression and function of Tim-3 on TIL CD4+ T cells and TIL CD8+ T cells in RCC patients.
- To determine the impact of Tim-3 expression on the functional status of TILs in RCC.
Main Methods:
- Analysis of Tim-3 expression on TIL CD4+ and CD8+ T cells from 30 RCC patients.
- Assessment of key transcription factors (GATA-3, T-bet) and cytokine (IFN-γ) expression in Tim-3+ TILs.
- Investigation of signaling pathways (Stat5, p38) in Tim-3-expressing TILs.
- Functional assays involving Tim-3 pathway blockade to evaluate T cell proliferation and IFN-γ production.
Main Results:
- Tim-3 expression was significantly increased on both TIL CD4+ and CD8+ T cells in RCC, correlating with higher cancer stages.
- Tim-3+ TILs exhibited down-regulation of GATA-3 and IFN-γ, and up-regulation of T-bet, indicating dysfunctional Th1/Tc1 cells.
- Impaired Stat5 and p38 signaling pathways were observed in Tim-3-expressing TIL CD8+ T cells.
- Blocking Tim-3 pathway restored T cell proliferation and enhanced IFN-γ production in TILs from RCC patients.
Conclusions:
- Tim-3 expression is associated with immune dysfunction in TILs within the RCC tumor microenvironment.
- Tim-3 represents a potential therapeutic target for augmenting anti-tumor immune responses in RCC.
- Targeting Tim-3 may offer a novel strategy to improve immunotherapy efficacy in renal cell carcinoma.
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