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Figure 3 4.2 Necroptosis promotes antigen cross-presentation and durable immunity Restoration of necroptotic signaling in melanoma, either through epigenetic modifier inhibitors to reverse RIPK3/MLKL silencing or direct small-molecule activation of the RIPK1/RIPK3/MLKL axis, enhances tumor cell immunogenicity by amplifying DAMP release and antigen cross-presentation, a phenomenon that has been validated in both in vitro melanoma cell models and in vivo syngeneic melanoma mouse models ( Importantly, necroptosis-induced antigen cross-presentation not only enhances the initial anti-tumor immune response but also contributes to the generation of memory T cells, which provide long-lasting immune surveillance and protection against tumor recurrence ( Furthermore, necroptosis-associated DAMPs can modulate the tumor microenvironment (TME) by recruiting and activating various immune effector cells, including natural killer (NK) cells and macrophages, which further amplify anti-tumor immunity ( In summary, necroptosis in melanoma serves as a potent immunogenic cell death modality that enhances antigen cross-presentation by DCs and fosters durable CD8+ T cell-mediated immunity

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