Fig. 2

Tumor cells employ multiple mechanisms to evade T-cell killing. (Figure created with BioRender.com). Tumor cells significantly attract T-cell infiltration through interactions, such as CXCL10-CXCR3 and CXCL16-CXCR6, as well as complement factors (e.g., C3-C3AR1). Additionally, they can evade immunity through immunosuppressive interactions with T cells, such as PDL1-PD1, PVR-TIGIT, and LGALS9-TIM3. Tumor cells can express genes responsive to TGF-β, including TGFBI, CTGF, and BHLH-E40, which activate the TGF-β pathway to induce epithelial-mesenchymal transition (EMT), inhibiting T-cell infiltration. Similarly, the FAM83H gene can serve a similar role. Tumor cells may inhibit CD8 + T-cell recruitment by reducing FAT2 gene expression, as well as negatively regulating chemokines such as CCL2, CCL3, CCL4, CCL19, CXCL10, and CXCL11 through various mechanisms. Additionally, they may overexpress CLDN3, which inhibits the expression of MHC-I and CXCL9, reducing CD8⁺ T-cell infiltration in tumor tissue. Furthermore, tumor cells can decrease T-cell infiltration and enhance T-cell depletion by activating HIF1a