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Figure 3. Mechanisms related to strategies for overcoming immunotherapy resistance. Immunotherapy, in combination with other treatments, constitutes the principal response strategy in clinical treatment. Chemotherapy can inflict DNA molecular damage upon tumor cells, thereby suppressing tumor growth and even eliminating tumor cells. The combination of immunotherapy with chemotherapy can augment the formation of new antigenic complexes, promote the immunogenicity of cancer cells, induce immune cell death, and modify the cytokine environment within the TME. Anti-angiogenic drugs exert immunomodulatory effects within the TME. They can reverse the immunosuppression caused by tissue hypoxia and immunosuppressive cells and enhance the maturation of DCs, as well as the transport and function of T cells. Tumor cell vaccines can effectively activate T cells and upregulate IFN-γ, IL-4, and IL-12, which result in good immunotherapeutic effect. Small-molecule drugs can enhance the antitumor cytotoxicity of M1 macrophages, and when combined with anti-PD-L1, they can enhance T cell activation, efficacy and inhibit tumor growth. Nanomedicine alleviates the physical properties of the TME and promotes the release of CD8⁺ T cells. Treatment efficacy can be enhanced when epigenetic modifiers are used with PD-1 inhibitors and aromatase inhibitors with pembrolizumab. Figure was created with Biorender.com. TME: Tumor microenvironment; DCs: dendritic cells; PD-L1: programmed cell death-ligand 1; PD-1: programmed death-1; ICIs: immune checkpoint inhibitors; EZH2: enhancer of zeste homolog 2.