Figure 3.

Mechanisms of immune evasion in the tumor microenvironment

Within the tumor microenvironment, tumor cells employ various mechanisms to evade immune surveillance and elude immune-mediated destruction. These mechanisms include: 1) Tumor-induced Dysfunction of Dendritic Cells: Tumor cells overexpress cytokines such as IL-6 and IL-10, while downregulating CCL4, which leads to the impairment of dendritic cell function. Additionally, tumor cells can weaken the antigen presentation ability of antigen-presenting cells by downregulating tumor antigen cross-presentation and MHC I expression. This inhibits T cell activation and suppresses the differentiation of CD8⁺ T lymphocytes into cytotoxic T lymphocytes, thereby reducing the killing effect. 2) Immunosuppressive Effects of TAMs: TAMs suppress T cell function by upregulating the expression of immune checkpoint molecules such as PD-1/PD-L1. They also secrete immunosuppressive cytokines like IL-10, TGF-β, and CXCL8, which not only regulate CD4⁺ T lymphocytes but also activate Tregs. TAMs can enhance Treg proliferation and inhibit T cell function through various mechanisms involving FoxP3, CTLA-4, TGF-β, IL-10, and IL-35. 3) MDSCs-Mediated Immune Suppression: MDSCs induce dysfunction in T cells by utilizing enzymes such as IDO and Arg-1. They also recruit Tregs by upregulating the expression of IL-10 and TGF-β. Additionally, Tregs activate MDSCs through the secretion of FoxP3, CTLA-4, TGF-β, IL-10, and IL-35, further contributing to immune suppression within the tumor microenvironment. Abbreviations: APC, Antigen-presenting cells; Arg-1, Arginase-1; CTL, Cytotoxic T lymphocytes; CCLA4, CC-chemokine ligand 4; CXCL8, also known as interleukin-8 (IL-8); DC, Dendritic cells; IDO, Indoleamine 2,3-dioxygenase; MDSCs, Myeloid-derived suppressor cells; TAMs, Tumor-associated macrophages; TGF-β, Transforming growth factor β.