Cisplatin-induced Pyroptosis Enhances the Efficacy of PD-L1 Inhibitor in Small-Cell Lung Cancer via GSDME/IL12/CD4Tem Axis
Wendi Xuzhang, Tingting Lü, Weiqiu Jin, Yongfeng Yu, Ziming Li, Lan Shen, Xiaomin Niu, Xinghao Ai, Liliang Xia, Shun Lü
Abstract
. Mechanically, cisplatin induced the activation of GSDME and the release of cytokines including IL-12, which enhance the expression of IFN-γ in T cells in the tumor immune microenvironment (TME) and subsequently improve anti-PD-L1 response. Altogether, our work demonstrates that cisplatin could induce GSDME-dependent cell pyroptosis to improve the response of anti-PD-L1 therapy though switching the TME from "cold" to "hot" in SCLC, indicating GSDME as a response biomarker for combination therapy of anti-PD-L1 and chemotherapy, as well as a potential target to sensitize the response to PD-L1 inhibitor therapy in future.
Topics & Concepts
CisplatinPyroptosisCancer researchIn vivoImmune systemChemotherapyImmune checkpointLung cancerApoptosisOncologyImmunotherapyMedicineChemistryInternal medicineProgrammed cell deathImmunologyBiologyBiochemistryBiotechnologyInflammasome and immune disordersPhagocytosis and Immune RegulationCancer Immunotherapy and Biomarkers