Figure 1.

Overview of T-cell immunity against tumors. A) Tumor antigens are recognized by DCs, which activate naïve T cells and stimulate the generation of antigen-specific cytotoxic CD8⁺ T cells and helper CD4⁺ T cells. CD8⁺ T cells release PFN and GZMB to induce cancer cell apoptosis. CD4⁺ T cells secrete cytokines such as IFN-γ and TNF-α, enhancing CD8⁺ T cell cytotoxicity and promoting macrophage activation and B cell-mediated humoral immunity. B) Tumors evade immune surveillance through multiple mechanisms. They upregulate inhibitory molecules like PD-L1, which engage co-inhibitory receptors such as CTLA-4 on CD8⁺ T cells, thereby suppressing their effector functions. Additionally, tumors downregulate MHC class I molecules, reducing the ability of CD8⁺ T cells to recognize tumor antigens via TCR, leading to impaired recognition and elimination of cancer cells. Tumor-secreted cytokines, including IL-6, TGF-β, and IL-10, further inhibit the activity of CD8⁺ T cells and NK cells. These cytokines, along with IL-35, also promote the proliferation of Tregs, which play a crucial role in suppressing anti-tumor immune responses, further enabling tumor immune evasion. C) Strategies include CAR T cells and TCR-engineered T cells to enhance the number and affinity of tumor-reactive T cells. Immune checkpoint inhibitors such as pembrolizumab and atezolizumab restore T cell activity by counteracting the immunosuppressive TME. Additional approaches focus on improving T cell infiltration, persistence, and combining therapies for synergistic effects against cancer. The images in the figures were created using BioRender (https://www.biorender.com/).