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Suppressive immune profile in combined positive score positive head and neck cancer patients treated with immunotherapy.

e18014 Background: Immunotherapy has revolutionized the landscape of systemic treatment of recurrent or metastatic (R/M HNSCC). However only a small percentage of patients achieve long-term benefit regarding overall response and overall survival from the current immunotherapy. Indeed it has already been demonstrated that HNSCC microenviroment is distinctly immunosuppressive due to the high concentration of several biomarkers such as regulatory T cells (Treg cells) and lymphocyte activation gene 3 (LAG3) . The aim of our study is to investigate if the expression of peculiar biomarkers can affect the therapeutic efficacy of anti-PD-1. Methods: Data from 35 patients with combined positive score (CPS) positive R/M HNSCC receiving first line immunotherapy or immunotherapy in association with chemotherapy, from March 2021 to November 2021 were prospectively reviewed. Treg cells, stromal and intratumoral, and LAG3 expression by cancer cells and CPS expression were evaluated on pre-treatment biopsies. We defined an immune suppressive profile (ISP) as a concomitant presence both of LAG3 and Treg cells. We evaluated the associations between early progression (EP), defines as progression occurred within 3 months, progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and the expression of LAG3 and with the ISP. Results: Twenty-four patients were male (69%), 11 female (31%) and median age was 67 years. Baseline ECOG PS, evaluated before the start of treatment, was 0, 1, and 2 in 14 (40%), 14 (40 %) and 7 (20%) patients, respectively. The primary tumor site was the oral cavity in 19 patients (54 %), the larynx in 13 patients (37 %), hypopharynx in 2 patients (6 %) and sinus in the remaining 1 (3%). Thirteen (37%) patients received pembrolizumab alone while pembrolizumab in association with chemotherapy (carboplatin or cisplatin and 5-fluorouracil) were administered intravenously to 22 (63%) patients. Twenty-eight (80%) patients presented LAG3 expression, whereas Treg cells was reported in the stroma and the tumour in 31 (89%) and 29 (83%) patients respectively. Twenty-three (66%) patients presented both expression of LAG3 and presence of Treg cells. We showed both a statistically significant association between LAG3 expression and EP disease ( p = 0.005) and between ISP and EP ( p = 0.023). We didn’t observed associations between PFS, OS, ORR and LAG3 and Treg status. Conclusions: Our findings showed that in CPS positive R/M HNSCC patients the contemporary expression of Treg cells and LAG3 could better select the patients primary resistant to anti-PD-1. The results of our study identify a novel immunological patients’ profile.