HLA-DR Expression in Paired Epithelial and CAFs Cell Line Cultures from Human Primary HPV-Negative Oral Squamous Cell Carcinoma: New Immunomarker in Head and Neck Tumors

Objective: Oral squamous cell carcinoma (OSCC) is a prevalent form of head and neck squamous cell carcinoma (HNSCC). Traditional treatments include surgery and radiotherapy/chemotherapy, but these often have limited efficacy. Immunotherapy has emerged as a promising treatment option. Recognition of novel biomarkers for immune checkpoints modulation could be helpful for establishing a personalized treatment for OSCC patients. Recently we showed that HNSCC epithelial cells acquire the ability to express class II MHC, HLA-DR. We aimed to investigate HLA-DR role in relation to the presence of the tumor microenvironment represented by CAFs. In addition, since programmed death-ligand 1 protein (PD-L1) is a critical target for cancer immunotherapy in HNSCC, we evaluated HLA-DR and PD-L1 level in healthy and OSCC tissues. Methods: Biopsy specimens from five OSCC patients were used to isolate tumor cells, normal fibroblast and CAFs. HLA-DR expression was evaluated. Cancer Genome Atlas database was used to evaluate HLA-DR and PD-L1 level in normal tissues and HNSCC derived biopsies. Results: Epithelial cancer cells showed de-novo HLA-DR expression. Importantly, HLA-DR expression was observed in both CAFs and normal fibroblasts with a significant higher level in CAFs. Atlas analysis showed an increase of HLA-DR and PD-L1 expression in HNSCC derived biopsies vs normal tissues and a positive correlation between HLA-DR and PD-L1 in cancer samples. Conclusions: Our findings highlighted that tumoral environment could affect OSCC cells inducing HLA-DR expression in non-APC tumoral and CAFs cells. The correlation between PD-L1 and HLA-DR expression has been observed, providing useful insights in targeted immunotherapy strategies for OSCC management.