CIT tumor lines: A novel series of immunogenic squamous cell skin carcinoma cell lines derived from chemical carcinogenesis

Immunotherapy is now widely used to treat cancer, but its efficacy in many cancer types remains modest. To overcome current barriers, preclinical mouse models that faithfully recapitulate the diversity of cancer types, tumor genetics, mutation burdens, and neoantigen patterns of human tumors are essential. Currently, there are relatively few transplantable murine models of squamous cell carcinomas (SCC). Here we describe a novel series of 11 skin SCC tumor lines, the Carcinogen-Induced Tumor (CIT) lines, syngeneic to the FVB strain. The CIT lines were established from skin carcinomas induced by DMBA and TPA treatment, and harbor genetic drivers and overall tumor mutational burdens that recapitulate those found across multiple human SCCs. Each CIT line gives rise to tumors with a consistent immune infiltration pattern, ranging from T cell-rich “hot” tumors to T cell-poor “cold” tumors. Hot CIT lines exhibit partial responses to treatment with immune checkpoint inhibitors, and we have identified two neoantigens present in an immunotherapy-responsive CIT line. The CIT lines thus provide a valuable new series of preclinical models for studying anti-tumor immune responses and developing strategies to improve immunotherapy efficacy in SCCs.