Upregulated 4-1BB (CD137) expression on skin T cells from a mouse model of precancerous skin

Abstract

Abstract Non-melanoma skin cancer (NMSC), including both squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), is a commonly diagnosed cancer in Australia. The role of the immune system in the development of NMSC is still poorly understood. Using a mouse model of precancerous, hyperplastic skin, we have investigated the expression and targeting of the T cell co-stimulatory molecule, 4-1BB (CD137). Our data shows that 4-1BB is expressed on both CD8 and non-CD8 T cells isolated from precancerous mouse skin with limited expression on T cells in normal skin or skin-draining lymph nodes. In contrast, the ligand for 4-1BB, 4-1BBL, was poorly expressed in skin and draining lymph nodes from precancerous or normal skin. Intradermal injection of antibodies against 4-1BB was more effective at labelling target cells within the hyperplastic skin than intravenous injection. Agonist antibodies against 4-1BB showed some enhancement of skin T cell function in vitro. The data suggests that 4-1BB expression is upregulated on T cells within precancerous mouse skin and may represent a promising target for immunotherapy against precancerous skin lesions.