AXL expression reflects tumor-immune cell dynamics impacting outcome in non-small cell lung cancer patients treated with immune checkpoint inhibitor monotherapy.

AXL receptor expression is proposed to confer immune-checkpoint inhibitor (ICI)-resistance in non-small cell lung cancer (NSCLC) patients. We sought to interrogate AXL expression in conjunction with mutational and tumor-microenvironmental features to uncover predictive mechanisms of resistance in ICI-treated NSCLC patients. Tumor samples from 111 NSCLC patients treated with ICI-monotherapy were analyzed by immunohistochemistry for tumor- and immune-AXL expression. Subsets of patients were analyzed by whole-exome sequencing (n = 44) and imaging mass cytometry (n = 14). Results were related to ICI-outcome measurements. Tumor-cell AXL expression correlated with aggressive phenotypic features including reduced OS in patients treated with ICIs ( Tumor-cell AXL-upregulation correlated with distinct oncotypes and microenvironmental immune-profiles that define chemotherapy-induced mechanisms of ICI-resistance, which suggests the combination of AXL inhibitors with current chemoimmunotherapy regimens can benefit NSCLC patients.

Informations de copyright

Copyright © 2024 Rayford, Gärtner, Ramnefjell, Lorens, Micklem, Aanerud and Engelsen.

Déclaration de conflit d'intérêts

JL and DM are founders of BerGenBio ASA. JL and AR were previously employed by BerGenBio ASA, and DM is currently employed by BerGenBio ASA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.