Circulating CD137+ T Cell Levels Are Correlated with Response to Pembrolizumab Treatment in Advanced Head and Neck Cancer Patients

Abstract

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.

CD137+ and regulatory T cells as independent prognostic factors of survival in advanced non-oncogene addicted NSCLC patients treated with immunotherapy as first-line

“…In metastatic renal carcinoma, CD137 + T cells were associated with the clinical response to tyrosine kinase inhibitors [ 23 , 24 ]. We recently demonstrated that the amount of circulating CD137 + T cells had a predictive and prognostic role in survival in advanced head and neck squamous cell carcinoma (HNSCC) patients treated with pembrolizumab as first-line therapy [ 15 ]. In another study carried out on 109 patients with different solid tumors under anti-PD1 treatment, we demonstrated and validated that high levels of CD137 + T cells were a prognostic factor of PFS and OS.…”

“…The ratio of regulatory T cells (Tregs) to Lox1 + -PMN-MDSCs predicted the response in Nivolumab-treated NSCLC patients [ 13 ]. We recently demonstrated the predictive and prognostic role of CD137 + T cell subset in solid tumors, including NSCLC, under anti-PD1 treatment [ 14 , 15 ]. This population was recognized as naturally occurring antigen-specific T cells and was associated with the wellness of the immune system [ 14 , 16 ].…”