2023 North America Conference on Lung Cancer (NACLC) - Posters and Abstracts-PP01.62 (Poster) Downregulation of Immune-Mediated Pathways in Lung Andenocarcinoma with KEAP1 or STK11 Mutation

PP01.62 (Poster) Downregulation of Immune-Mediated Pathways in Lung Andenocarcinoma with KEAP1 or STK11 Mutation

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A study conducted by researchers at the University of Missouri-Kansas City School of Medicine and the Inova Schar Cancer Institute aimed to explore the immune profiles of patients with lung adenocarcinoma who had mutations in the KEAP1 or STK11 genes. These genes have been associated with worse survival outcomes in observational studies, but the mechanism of immune checkpoint inhibitor (ICI) resistance is still unclear.<br /><br />The analysis included 510 patients from The Cancer Genome Atlas (TCGA) cohort and 229 patients from the Stand Up To Cancer (SU2C) cohort. The results showed that patients with KEAP1 mutations had consistent downregulation in various immunologic pathways compared to those without mutations. This downregulation included complement activation, humoral immune response, antigen receptor-mediated signaling, and B-cell-mediated pathways. The mutational status of KEAP1 also aligned with differential gene expressions.<br /><br />However, the study did not find a predictive association between KEAP1 or STK11 mutations and a worse response to ICI therapy. The mutated KEAP1 or STK11 genes were not significantly associated with poorer overall survival in both cohorts. The STK11-deficient phenotype also did not have worse overall survival or progression-free survival.<br /><br />The findings suggest that while KEAP1 mutations may result in the downregulation of immunologic pathways, they are not predictive of inferior response to ICI therapy. Further studies are needed to understand the major pathway to reverse the immune downregulation.<br /><br />In conclusion, this study provides insights into the immune profiles of patients with lung adenocarcinoma with KEAP1 or STK11 mutations. However, the mutations themselves do not appear to be predictive of a worse response to ICI therapy.

Asset Subtitle

Ben Ponvilawan

Keywords

University of Missouri-Kansas City School of Medicine

Inova Schar Cancer Institute

lung adenocarcinoma

KEAP1 gene

STK11 gene

immune profiles

immune checkpoint inhibitor resistance

The Cancer Genome Atlas

Stand Up To Cancer

immunologic pathways