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. 2023 Jun 16;14:1204363. doi: 10.3389/fimmu.2023.1204363

Figure 5.

Figure 5

Combined strategies for improving exhausted CD8+ T cells. Strategies including 4-BB activation, epigenetic therapy, metabolism-based therapy and cytokine therapy cooperate with PD1/PDL1 blockade and markedly increase anti-tumor immunity. Combination of 4-BB activation and PD1/PDL1 blockade promotes greater number of terminally exhausted subsets with improved cytotoxicity. Combination of epigenetic therapy and PD1/PDL1 blockade leads to a further Tpex expansion and enhanced effector function of TEXs. Combination of metabolism-based therapy and PD1/PDL1 blockade further increases the cytotoxicity of terminally exhausted subsets. Combination of cytokine therapy and PD1/PDL1 blockade effectively enhances anti-tumor response in different ways. Programmed cell death protein 1 (PD1); Programmed cell death ligand 1 (PDL1); Interleukin-10-Fc fusion protein (IL-10/Fc); Interferon regulatory factor 2 (IRF2); Thymocyte selection-associated high mobility group box protein (TOX).