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.

Keywords: 4-1BB; CD137; HNSCC; anti-PD1; immunotherapy.

Figure 1

CD137⁺ T cells are correlated with response to anti–PD–1 treatment and patient survival. (A) The scattered dot plot shows the values of CD3⁺CD137⁺ cells in responder (R) and non–responder (NR) patients ± standard deviation (SD). The horizontal lines correspond to the median values of CD3⁺CD137⁺ lymphocytes of the two groups. (B) The scattered dot plot represents the values of CD3⁺CD137⁺ cells in patients with (Yes) or without (No) comorbidities. The horizontal lines correspond to the median values of CD3⁺CD137⁺ lymphocytes of the two groups. (C) Kaplan–Meier curves for PFS and OS were used to determine 1.65% as the cut-off of circulating CD3⁺CD137⁺ cells wherein patients with a percentage ≥1.65% showed prolonged survival. (D) Kaplan–Meier curves for PFS and OS considering the score related to performance status (PS) (PS = 0 vs. PS1 = 1, 2). Patients with PS = 0 showed a longer PFS and OS than those with PS = 1, 2. m = Months; NR = not yet reached.