Quantitative assessment of CMTM6 in the tumor microenvironment and association with response to PD-1 pathway blockade in advanced-stage non-small-cell lung cancer

Abstract Introduction CMTM6 has been described as a PD-L1 regulator at the protein level by modulating stability via ubiquitination. In this study, we describe the patterns of CMTM6 expression and assess its association with response to PD-1 pathway blockade in non-small-cell lung cancer (NSCLC). Methods We used multiplexed quantitative immunofluorescence to determine the expression of CMTM6 and PD-L1 in 438 NSCLCs represented in tissue microarrays, including two independent retrospective cohorts of immunotherapy treated (n = 69) and untreated (n = 258) patients, and a third collection of EGFR and KRAS genotyped tumors (n = 111). Results Tumor and stromal CMTM6 expression was detected in approximately 70 % of NSCLCs. CMTM6 expression was not associated with clinical features or EGFR/KRAS mutational status and showed a modest correlation with T-cell infiltration (R2 Conclusion This study supports the mechanistic role for CMTM6 in stabilization of PD-L1 in patient tumors and suggests that high co-expression of CMTM6 and PD-L1, particularly in stromal immune-cells (macrophages), might identify the greatest benefit from PD-1 axis blockade in NSCLC.