Genomic and immune landscape of recurrent and/or metastatic squamous cell carcinoma of the head and neck progressing on anti-PD1 treatment

Anti-PD1 therapies improve survival in recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN), but only a minority of patients achieve durable responses. The mechanisms driving resistance to anti-PD1 in SCCHN remain poorly understood. Using the IMMUcan multi-omics workflow, we characterized the molecular and immune profiles of R/M SCCHN progressing on anti-PD1 treatment and compared them to an anti-PD1-naïve cohort. Tumor biopsies from anti-PD1 resistant SCCHN patients exhibited significantly more EGFR and MYCL amplifications, along with increased MYC pathway alterations. Transcriptomic and proteomic analyses revealed that anti-PD1 secondary resistant SCCHN had increased CD8+ T cell infiltration with higher levels of immune exhaustion markers than primary resistant and naïve SCCHN. Additionally, high B2M expression correlated with greater T cell infiltration and improved survival following anti-PD1 therapy. Tumor cell B2M expression was independent of TMB and PD-L1 expression, suggesting that B2M expression could serve as an additional biomarker for anti-PD1 response.