084 Neoantigen-specific T cell responses constrain cutaneous squamous cell carcinoma

The role of neoantigens in generating T cell responses that control cutaneous squamous cell carcinoma (cSCC) is unknown. To investigate this, solar UV-induced invasive cSCC tumors were used to create clonal cSCC cell lines on the BALB/c background. These cSCC cell lines constitutively express MHC class I, and thus, can be targeted for destruction by CD8 T cells. Intradermal injection of these cSCC cells reliably forms tumors in wild-type mice. cSCC tumors grow faster in athymic mice, lacking mature T cells, compared to wild-type mice, supporting that T cells constrain cSCC growth. Both CD8 and CD4 T cells, expressing granzyme B+ and IFN-γ+, infiltrate cSCC tumors. Mice depleted of CD8 or CD4 T cells alone have increased cSCC tumor growth, and mice depleted of both CD8 and CD4 T cells have the fastest tumor growth, demonstrating a role for CD8 and CD4 T cells in controlling cSCC growth. Vaccination with irradiated cSCC cells completely protects from tumor challenge, and this response is dependent on CD8 T cells. Vaccination with irradiated tumor cells from another solar UV-induced cSCC cell line does not protect from tumor challenge, demonstrating that vaccination-induced protection is not due to a shared antigen. Whole exome and RNA sequencing was performed on the two cSCC cell lines. To identify neoantigens anticipated to elicit T cell responses, missense mutations were prioritized based on the predicted binding affinity, presentation on MHC, and expression. The two cSCC cell lines do not share any prioritized neoantigens, supporting that the response to vaccination is neoantigen specific. These results support that neoantigen-specific T cells constrain cSCC growth in a solar UV-induced model. This model will enable the identification of neoantigen features that promote tumor rejection.