Longer OS and RFS for CD3high/PD-L1+ head and neck squamous cell carcinoma (HNSCC) patients

BackgroundT cell infiltrates are associated with longer survival in HNSCC. For PD-L1 expression, aside of treatment targeting the PD1/PD-L1 axis, published data are equivocal. In this analysis, we combined CD3 density and PD-L1 expression in a cohort of HNSCC patients treated with surgery and risk-adapted adjuvant therapy.MethodsIHC for CD3 and PD-L1 (E1L3N) was performed in a TMA with 457 HNSCC (triplicates). Digital image analysis (QuPath) was performed to measure CD3 densities (cells/mm2). PD-L1 expression was assessed in tumor and immune cells analogue to CPS. Overall survival (OS) and recurrence-free survival (RFS) in months were calculated using the Kaplan-Meier method and were compared by log-rank tests. A multivariable cox regression analysis was performed for T-, N-, HPV-status and CD3/PD-L1 (hot vs. cold).ResultsCD3 densities compared by primary tumor site were significantly different, whereas PD-L1 CPS were not. Median CD3 density of the respective primary site was used for binarization (CD3high/low). 343 patients (pt) were evaluable for OS and 324 for RFS. CD3high pt had longer median OS (p<0.001; not reached vs. 52.0 Mo) and RFS (p<0.001; 111,3 vs. 43.3 Mo) compared to CD3low. Pt with PD-L1 expression CPS=1-19 and CPS20 had longer OS (p=0.009) and longer RFS (p=0.019) than pt with CPS<1 (CPS=1-19 vs CPS20 = ns). Binarization by CPS1 resulted in longer median OS (p=0,002; 111,3 vs. 49,3 Mo) and RFS (p=0.006; 98.3 vs. 41.0 Mo) compared to CPS<1. OS and PFS were significantly longer for CD3high/CPS1 compared to all other combinations (p<0.001). CD3low/CPS<1, CD3low/CPS and CD3high/CPS<1 did not differ significantly for OS or RFS. CD3high/CPS1 (hot) was grouped against CD3low/CPS<1, CD3low/CPS and CD3high/CPS<1 combined (cold). In a multivariable cox regression for OS, N-status (hazard ratio (HR) = 1.95), HPV-status (HR = 0.422) and “hot� (HR = 0.403) were independent prognostic markers. For RFS only “hot� was an independent prognostic marker (HR = 0.526).ConclusionsThe combination of CD3-density and PD-L1 expression performed superiorly in comparison to CD3 or PD-L1 alone. This may explain the equivocal impact of PD-L1 on OS and RFS. CD3-density combined with PD-L1 expression may identify patients who could benefit most from immunotherapy.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureS. Laban: Financial Interests, Institutional, Advisory Board: Merck Sharp & Dohme, Bristol Myers Squibb, Sanofi Genzyme; Financial Interests, Institutional, Invited Speaker: Merck Sharp & Dohme, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Institutional, Other, patent for an oropharyngeal cancer multi-peptide vaccine (pending): filed patent (patent pending); Non-Financial Interests, Principal Investigator: Immutep, Merck Sharp & Dohme, Bristol Myers Squibb, ISA-Pharmaceuticals. R. Remark: Financial Interests, Personal, Other, Employee: Innate Pharma. All other authors have declared no conflicts of interest.