This retrogenic model can be employed to define self-tolerance mechanisms restricting T and B cell responses to GUCY2C to optimize colorectal cancer immunotherapy without autoimmunity.
The colorectal cancer antigen GUCY2C exhibits unique split tolerance, evoking antigen-specific CD8<sup>+</sup>, but not CD4<sup>+</sup>, T-cell responses that deliver anti-tumor immunity without autoimmunity in mice.
In that context, guanylate cyclase C (GUCY2C) is an established biomarker and therapeutic target for metastatic colorectal cancer with immunological characteristics that promote durable antitumor efficacy without autoimmunity.