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Brutten, M.D.

10.1200/JCO.2012.43.3391 51 CuriglianoG.PivotX.CortsJ.EliasA.CesariR.KhosravanR.et al (2013)

Induction of ferroptosis can synergize with immune checkpoint inhibitors (ICIs) by reshaping the TME towards a more immunogenic state, overcoming resistance mechanisms ( 3 Activation pathways of pyroptosis in melanoma and its pro-inflammatory effects Pyroptosis, as a unique form of regulated inflammatory cell death, has emerged as a pivotal regulatory node in the progression of melanoma and the efficacy of antitumor therapies ( 3.1 Gasdermin protein-mediated execution mechanism of pyroptosis Pyroptosis is a form of regulated inflammatory cell death primarily executed by the gasdermin (GSDM) family of proteins, which includes members such as GSDMD and GSDME ( Figure 2 ) ( Figure 2 3.2 Pyroptosis-associated inflammatory cytokine release and antitumor immune activation The formation of gasdermin pores during pyroptosis leads to a characteristic cellular swelling and eventual rupture of the plasma membrane, resulting in the release of pro-inflammatory cytokines such as interleukin-1 (IL-1) and interleukin-18 (IL-18) ( 4 Signal transduction of necroptosis and its role in immune memory in melanoma Melanoma, a highly aggressive cutaneous malignancy characterized by remarkable heterogeneity and immune evasion capacity, remains a major clinical challenge despite advances in immunotherapeutic strategies ( 4.1 RIPK1/RIPK3/MLKL signaling axis and necrosome formation Necroptosis, a regulated form of necrotic cell death, is orchestrated by a signaling cascade involving receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL) ( In the context of melanoma, the necroptotic pathway is frequently dysregulated

Science 290: 15711574 Weissman JS, Kim PS (1993) Effcient catalysis of disulphide bond rearrangements by protein disulphide isomerase