Figure 6.

Schematic diagram summarizes genes/functions that are upregulated or downregulated in CD4⁺TIM-3⁺ T cells in the colorectal tumor microenvironment. In the colorectal TME, CD4⁺TIM-3⁺ cells co-express genes including FoxP3, Helios, PD-1, and CTLA-4 to suppress anti-tumor immune responses. Our study showed that DNA replication and cell cycle genes were downregulated, while genes related to immune suppression, cell proliferation, T-cell exhaustion, carcinogenesis, migration, and metastasis were upregulated in CD4⁺TIM-3⁺, compared with CD4⁺TIM-3⁻. Individual or combinational antibody therapies using anti-TIM-3, anti-PD-1, and anti-CTLA4 may target highly immunosuppressive TIM-3⁺ TILs to elicit anti-tumor responses in CRC.