PD-L1 and LAG-3 expression in advanced cutaneous squamous cell carcinomas

Expression of programmed death ligand 1 (PD-L1) by cutaneous squamous cell carcinomas has been shown to correlate with advanced disease and risk of metastasis. Lymphocyte activation gene 3 (LAG-3, or CD223) is an inhibitory receptor that interacts with the PD-L1 axis, which has been shown to be a marker of immune exhaustion and a potential immunotherapy target. However, the role of LAG-3 in cutaneous squamous cell carcinoma has not been established.

We reviewed 18 cases of locally advanced and/or metastatic cutaneous squamous cell carcinomas and assessed for PD-L1 expression, presence or absence of tumor-infiltrating lymphocytes (TILs), and expression of LAG-3 by TILs.

PD-L1 expression was present in 11 of 13 locally advanced primary tumors and 5 of 5 metastases. TILs were present in all 18 tumors, of which 14 cases were positive for LAG-3 expression. In positive cases, LAG-3 was expressed on average by 32% of TILs.

Advanced cutaneous squamous cell carcinomas frequently express PD-L1 and are associated with an inflammatory response. LAG-3 expression by TILs was identified in a majority of cases. Our findings suggest that LAG-3 positive tumor-associated inflammatory cells may play a role in the development of advanced disease and offer another potential target for drug therapy.