Advancing translational research for colorectal immuno-oncology

Abstract

Colorectal cancer (CRC) is a common and deadly disease. Unfortunately, immune checkpoint inhibitors (ICIs) fail to elicit effective anti-tumour responses in the vast majority of CRC patients. Patients that are most likely to respond are those with DNA mismatch repair deficient (dMMR) and microsatellite instability (MSI) disease. However, reliable predictors of ICI response are lacking, even within the dMMR/MSI subtype. This, together with identification of novel mechanisms to increase response rates and prevent resistance, are ongoing and vitally important unmet needs. To address the current challenges with translation of early research findings into effective therapeutic strategies, this review summarises the present state of preclinical testing used to inform the development of immuno-regulatory treatment strategies for CRC. The shortfalls and advantages of commonly utilised mouse models of CRC, including chemically induced, transplant and transgenic approaches are highlighted. Appropriate use of existing models, incorporation of patient-derived data and development of cutting-edge models that recapitulate important features of human disease will be key to accelerating clinically relevant research in this area.

Fig. 1. Colorectal cancer (CRC) mouse models used for immuno-oncology research.

These currently used CRC models include a chemically induced, b genetic, c transplant models and d patient-derived xenografts.

Fig. 2. The clinical relevance of colorectal cancer models in immunotherapy research compared to the practicality of their establishment.

Transplant (green), genetic (blue) and chemical (red) models are included.

Fig. 3. The future for immuno-oncology research using CRC mouse models.

Important considerations for advancing mouse models and translational research for colorectal immuno-oncology.