Tim-3 on Peripheral CD4⁺ and CD8⁺ T Cells Is Involved in the Development of Glioma

Abstract

Tim-3 acts as a negative regulatory molecule and plays a critical role in immune tolerance. The purpose of this study was to investigate the expression of Tim-3 on peripheral CD4⁺ and CD8⁺ T cells in glioma. A total of 30 newly diagnosed glioma patients and 30 healthy controls were recruited and leukocytes from peripheral blood mononuclear cells were analyzed for Tim-3 surface expression by flow cytometry. Plasma tumor necrosis factor-alpha (TNF-α) was also measured. Data showed that expression of Tim-3 was significantly increased in both CD4⁺ and CD8⁺ T cells in glioma patients than in controls (p<0.001 and p<0.001, respectively). Patients with a higher tumor grade revealed further elevated Tim-3 expression in CD8⁺ T cells compared with those with a lower tumor grade. Also, the Karnofsky score of patients was negatively correlated with the percentage of Tim-3⁺CD8⁺ T cells in glioma patients (p=0.007). In addition, an inverse correlation was observed between the plasma level of TNF-α and Tim-3⁺CD4⁺ T cells (p=0.005) or Tim-3⁺CD8⁺ T cells (p<0.001) in glioma patients. Our results suggested that Tim-3 may be involved in the development of glioma.

Combination Therapy with Anti-PD-1, Anti-TIM-3, and Focal Radiation Results in Regression of Murine Gliomas

“…In addition, a higher frequency of TIM3 + CD8 T cells was positively correlated with a higher tumor grade and negatively correlated with Karnofsky scores (13). In our in vivo experiments, we isolated BILs from the brains of orthotopic glioma-bearing mice and observed a significant increase in TIM-3 expression on brain-infiltrating CD4 and CD8 cells compared to naïve, non-tumor–bearing control animals.…”

“…However, clinical studies have demonstrated TIM-3 expression to be significantly elevated on both circulating blood lymphocytes and TILs in glioma patients. This expression was found to be positively correlated with glioma grade and negatively correlated with Karnofsky performance status score (13, 14). Using our glioma model, we hypothesized that dual blockade of PD-1 and TIM-3 would result in a more robust antiglioma immune response and improved survival compared with either antibody alone.…”

Recent advances and future of immunotherapy for glioblastoma

“…It has been shown to be highly expressed in patients with melanoma, NSCLC, lymphoma and other malignancies 74 . In recent investigations it was found that not only was TIM-3 expression significantly increased in peripheral blood CD4 + and CD8 + T cells of glioma patients compared with healthy controls, but that the expression of galectin-9 in tumor tissues was associated with TIM-3 expression on Tumor Infiltrating Lymphocytes (TILs) and the WHO grade of glioma 46, 75 . Some studies show that combination therapy with anti-PD-1, anti-TIM-3 and focal radiation results in regression of murine gliomas, concluding that the addition of a second checkpoint-blocking antibody could achieve additive or synergistic antitumor effects 76 .…”

Targeting immune checkpoints in malignant glioma

“…The significance of the TIM-3 has been demonstrated in different cancer models, including colon cancer, mammary carcinoma, and melanoma [99, 100]. In glioma patients, the expression of TIM-3 on CD4+T cells and CD8+T cells is significantly elevated than in healthy controls, and the higher expression level of TIM-3 on T cells is associated with tumors of higher grades [101]. …”