Back to article: Therapeutic potential of DNA methyltransferase inhibitors with immune checkpoint inhibitor therapy in breast cancer


FIGURE 1: Multiple mechanisms of DMTi potentiation of anti-tumor immuni-ty. First, DMTi treatment up-regulates baseline MHC-I expression and MHC-I expression in response to IFN-γ, thereby enhancing antigen presentation capacity and cytotoxic CD8+ T cell activation. Second, DMTi treatment increases Cxcr3 chemokine (i.e., Cxcl9, Cxcl10, Cxcl11) expression, thereby enhancing T cell trafficking to the tumor microenvironment. Third, DMTi treatment activates NFκB signaling, presumably through ERV dsRNA expression, initiating an innate immune response. Each of these mechanisms in toto likely contribute to enhanced response to ICI therapy.

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