2024 Asia Conference on Lung Cancer (ACLC) - Poster & ePosters-PP01.02

PP01.02 - Shihao Bao

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The study investigates the potential of salidroside, a small molecule drug, to enhance the effectiveness of immunotherapy in lung adenocarcinoma by targeting the IL4I1/Trp/AHR axis. Through in vivo mouse models resistant to anti-PD-1 therapy, the researchers identified a significant difference in IL4I1 expression between resistant and original tumors. IL4I1, known for its pro-tumorigenic and immunosuppressive roles in various cancers, was found to impact Trp catabolism significantly. Knockdown of IL4I1 reduced this catabolism, suggesting its role in resistance.<br /><br />The study reveals that salidroside inhibits IL4I1 promoter activity, which subsequently suppresses the AHR/Trp pathway. This inhibition leads to reduced AHR nuclear translocation and transforms the tumor microenvironment. By doing so, salidroside enhances the infiltration of CD4 and CD8 T-cells and slows tumor growth, effectively sensitizing tumors to anti-PD-1 therapy.<br /><br />Furthermore, the combination of salidroside and anti-PD-1 therapy resulted in significant tumor regression in mice. However, this therapeutic effect was lost when IL4I1 was overexpressed, indicating that salidroside's efficacy is contingent upon the presence of IL4I1.<br /><br />The results suggest salidroside as a promising adjunct in lung adenocarcinoma immunotherapy, offering a new strategy to overcome resistance to checkpoint inhibitors like anti-PD-1. This study highlights the importance of targeting metabolic pathways, such as the AHR/Trp pathway, to remodel the immune microenvironment and enhance therapeutic outcomes in cancer treatment.

Keywords

salidroside

lung adenocarcinoma

immunotherapy

IL4I1

Trp catabolism

AHR pathway

anti-PD-1 therapy

tumor microenvironment

CD4/CD8 T-cells

checkpoint inhibitors