Circulating CD137+ T cell levels are correlated with response to pembrolizumab treatment in advanced head and neck cancer patients

Pembrolizumab, an anti-PD-1 antibody, has been approved as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma ((R/M) HNSCC). However, only a minority of patients benefit from immunotherapy, which highlight the need to identify novel biomarkers to optimize treatment strategies. CD137+T cells have been identified as tumour-specific T cells cor-related with immunotherapy responses in several solid tumours. In this study, we investigated the role of circulating CD137+ T cells in (R/M) HNSCC patients undergoing pembrolizumab treatment. PBMCs obtained from 40 (R/M) HNSCC patients with a PD-L1 combined-positive-score (CPS)>1 were analysed at baseline via cytofluorimetry for the expression of CD137, and it was found that the percentage of CD3+CD137+ cells is correlated with the clin-ical benefit rate (CBR), PFS, and OS. The results show that levels of circulating CD137+ T cells are significantly higher in responder patients than in non-responders (p=0.03). Moreover, patients with CD3+CD137+ percentage >1.65% had prolonged OS (p=0.02) and PFS (p=0.02). Multivariate analysis, on a combination of biological and clinical parameters, showed that high levels of CD3+CD137+ cells (>1.65%) and performance status (PS)=0 are independent prognostic factors of PFS (CD137+T cells, p=0.007; PS, p=0.002) and OS (CD137+T cells, p=0.006; PS, p=0.001). Our results suggest that levels of circulating CD137+ T cells could serve as biomarkers for pre-dicting the response of (R/M) HNSCC patients to pembrolizumab treatment, thus contributing to the success of anti-cancer treatment.