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 highlights the need to identify novel biomarkers to optimize treatment strategies. CD137(+) T cells have been identified as tumour-specific T cells correlated 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 clinical 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 predicting the response of (R/M) HNSCC patients to pembrolizumab treatment, thus contributing to the success of anti-cancer treatment.