Dottorato in NETWORK ONCOLOGY AND PRECISION MEDICINE

Titolo della tesi: COMPREHENSIVE PROFILE IN HEAD AND NECK CANCER PATIENTS TREATED WITH IMMUNOTHERAPY

Immunotherapy has a fundamental role in the treatment of recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, not all the patients achieve long-term benefit in terms of overall response and survival. As a matter of fact, HNSCC has an immunosuppressive microenvironment caused by high levels of regulatory T cells and immunosuppressive molecules, such as LAG3 and CD73. Methods We reviewed data from 50 patients with R/M HNSCC receiving first line immunotherapy with or without chemotherapy based on a combined positive score (CPS). CD73 expression by cancer and immune cells was evaluated on pre-treatment and the percentage of stained cells was recorded. We focus our study on the association between CD73 expression on neoplastic and immune cells and early progression (EP), defined as progression occurring within 3 months. Results 88% of patients had the primary tumour site in the oral cavity or larynx. Patients underwent a therapy based on pembrolizumab associated in 40% of cases to chemotherapy. CD73 was positive in 82% and 96% of cases on neoplastic and immune cells, respectively. The median value of CD73 was 32% for neoplastic cells and 10% for the immune ones. We observed a significant association between CD73 expression over the median value and EP disease. There is no recorded correlation between the expression of CD73 on immune cells and early progression. Conclusions CD73 on neoplastic cells could predict resistance to immunotherapy in patients with CPS positive R/M HNSCC. The addition of this biomarker to routine evaluation of CPS could help to select patients primary resistant to anti-PD-1 immunotherapy.