Endogenous Immune Responses to Colorectal Cancer

Abstract

An ideal immunotherapy for colorectal cancer would target an endogenous tumour antigen. Endogenous antigens produce a more physiologically relevant immune response than model antigens traditionally used to study anti-tumour immune responses. CD8+ T cells play an important role in cancer control as they are cytotoxic and recognise antigens on target tumour cells. This study aims to develop a model of endogenous immune responses to an endogenous colorectal cancer antigen.

Lymphocytes responding to the endogenous antigen AH1 on the murine colon carcinoma CT26 were investigated in vitro using proliferation assays to measure expansion, flow cytometry to measure activation, and a pentamer to measure AH1-specificity. These results were incorporated into a mouse model of colorectal cancer, in vivo via a subcutaneous injection, and the response to endogenous AH1 antigen measured. CD25+ CD44+ and CD62Llow CD8 T cells increased in frequency and total number after two stimulations with AH1 peptide, indicating T cells were activated and undergoing clonal expansion. Pentamer staining revealed CD8+ T cells specific for this endogenous AH1 antigen. An even higher activation was seen when αCD3/28 was added to the primary stimulation. In vivo experiments also demonstrated CD8+ T cell responses to the AH1 peptide indicating this antigen can trigger an immune response, and therefore it is a potential target for immunotherapy applications. This research develops a physiologically relevant model of endogenous immune responses to an endogenous colorectal cancer antigen. AH1 is a possible target for immunotherapy. Data gained from this study brings us closer to immunotherapy development.