Prognostic significance of PD-L1 expression on circulating tumor cells in patients with head and neck squamous cell carcinoma

TLDR

PD‑1 checkpoint inhibitors require predictive biomarkers, yet circulating tumor cell (CTC) molecular profiling lacks such markers for head‑and‑neck squamous cell carcinoma. The study aimed to determine whether PD‑L1 overexpression in EpCAM⁺ CTCs could be detected at baseline and during therapy and used to predict clinical outcomes in HNSCC patients treated with curative intent. A highly sensitive RT‑qPCR assay quantified PD‑L1 mRNA in EpCAM⁺ CTCs from 113 locally advanced HNSCC patients at baseline, after two cycles of induction chemotherapy (week 6), and at the end of concurrent chemoradiotherapy (week 15). PD‑L1 overexpression in CTCs at the end of treatment was present in 22 % of patients, independently predicted shorter progression‑free and overall survival, was associated with a lower likelihood of complete response, and indicates that adjuvant PD‑1 inhibitors merit evaluation in this subgroup.

Abstract

Successful application of programmed death 1 (PD1) checkpoint inhibitors in the clinic may ultimately benefit from appropriate patient selection based upon predictive biomarkers. Molecular characterization of circulating tumor cells (CTC) is crucial for the investigation of molecular-targeted therapies while predictive biomarkers for response to PD1 checkpoint inhibitors are lacking. We sought to assess whether overexpression of PD-L1 in CTCs could be detected at baseline and at different timepoints during treatment in a prospective cohort of head and neck squamous cell carcinoma (HNSCC) patients and used to predict clinical outcome after treatment with curative intent.We developed a highly sensitive, specific and robust RT-qPCR assay for PD-L1 mRNA expression in EpCAM(+) CTCs. In a prospective cohort of 113 locally advanced HNSCC patients treated with curative intent we evaluated PD-L1 expression in the EpCAM(+) CTC fraction at baseline, after 2 cycles of induction chemotherapy (week 6) and at the end of concurrent chemoradiotherapy (week 15).PD-L1 overexpression was found in 24/94 (25.5%) patients at baseline, 8/34 (23.5%) after induction chemotherapy and 12/54 (22.2%) patients at the end of treatment. Patients with CTCs overexpressing PD-L1 at end of treatment had shorter progression-free survival (P = 0.001) and overall survival (P < 0.001). Multivariate analysis revealed that PD-L1 overexpression at end of treatment was independent prognostic factor for progression-free survival and overall survival. The absence of PD-L1 overexpression at the end of treatment was strongly associated with complete response with an odds ratio = 16.00 (95% CI = 2.76-92.72, P = 0.002).We demonstrate that detection of CTCs overexpressing PD-L1 is feasible and may provide important prognostic information in HNSCC. Our results suggest that adjuvant PD1 inhibitors deserve evaluation in HNSCC patients in whom PD-L1(+) CTCs are detected at the end of curative treatment.