CMTM6 and PD-L1 are independent prognostic biomarkers in head and neck squamous cell carcinoma

The predictive potential of immunological markers are not fully understood in head and neck squamous cell carcinomas (HNSCC). We retrospectively analyzed 129 treatment-naive HNSCCs for programmed death ligand 1 (PD-L1) and CKLF-like MARVEL transmembrane domain-containing 6 (CMTM6) expression, tumor-infiltrating leukocytes (TILs), and tumor-associated macrophages (TAMs). We evaluated mutual relationships among these markers, HPV-status, and overall survival (OS). PD-L1 and CMTM6 expression (combined positive score ≥ 1 and ≥ 5) was detected in ~ 75% of HNSCCs. The HPV-status had a minor impact on expression of either marker. Nearly all PD-L1-positive cases showed simultaneous CMTM6 expression in comparable staining patterns. Tumors with PD-L1 (p < 0.0001) and/or CMTM6 (p < 0.05) expression showed the best OS. A high density of TILs (p < 0.01), CD8 + T cells (p  1 had prognostic relevance. PD-L1 and CMTM6 correlated with density of TILs and CD8 + cells (Spearman r = range from 0.22 to 0.34), but not with HPV-status. Our results identify CMTM6 as an important interaction partner in the crosstalk between TILs, CD8 + T cells, and PD-L1, mediating anticancer efficacies. CMTM6 evaluation may be helpful for prognostic prediction and additionally serve as a reliable biomarker for selecting HNSCC patients eligible for ICIs treatment.