ILT4 inhibition prevents TAM- and dysfunctional T cell-mediated immunosuppression and enhances the efficacy of anti-PD-L1 therapy in NSCLC with EGFR activation
Xiaozheng Chen, Aiqin Gao, Fang Zhang, Zijiang Yang, Shuyun Wang, Yuying Fang, Juan Li, Jingnan Wang, Wenjing Shi, Linlin Wang, Yan Zheng, Yuping Sun
Abstract
ILT4 was induced by activation of EGFR-AKT and ERK1/2 signaling in NSCLC cells. Overexpressed ILT4 suppressed tumor immunity by recruiting M2-like TAMs and impairing T cell response, while ILT4 inhibition prevented immunosuppression and tumor promotion. Furthermore, ILT4 inhibition enhanced the efficacy of PD-L1 inhibitor in EGFR wild-type but not in EGFR mutant NSCLC. Our study identified novel mechanisms for EGFR-mediated tumor immune escape, and provided promising immunotherapeutic strategies for patients with EGFR-activated NSCLC.
Topics & Concepts
Cancer researchFlow cytometryImmune systemImmunotherapyPD-L1Immune checkpointBiologyMolecular biologyImmunologyCancer Immunotherapy and BiomarkersImmune cells in cancerImmune Cell Function and Interaction