‘Evaluating Immunotherapies In A Preclinical Model Of Metastatic Colorectal Cancer’

Daniele VF Tauriello, Jordi Badia Ramentol and Sergio Palomo Ponce, Institute for Research in Biomedicine (IRB)

This year there will be more than 700,000 deaths due to Colorectal Cancer (CRC) worldwide. The vast majority of these deaths will occur due to development of metastasis. Current therapeutic approaches do not cure metastatic disease in the majority of patients.

Therefore, there is an unmet need for novel strategies to target CRC at advanced stages. Amongst the most promising therapeutic strategies to aggressive cancers are immunotherapies, which are providing multiple stories of durable full remissions in otherwise incurable cancers such as lung cancer or advance melanoma. Progress to understand to what extent patients with metastatic CRC could benefit from immunotherapy is currently limited by lack of good preclinical models.

Despite this, there have been a few clinical studies in CRC showing only a mild response in microsatellite instable tumors which only account for 15% of all CRCs. We have developed the first mouse model for metastatic CRC in a fully immunocompetent setting. It reproduces many of the features of human CRCs and is microsatellite stable.

In this proposal, we aim to exploit this model system to test the effectiveness of immunotherapies against CRC. Specifically the project has two objectives: i: to characterize in detail the immune landscape of CRC tumors and dissect those cell types involved in immune detection/escape during metastasis. This is important for the design of effective immunotherapies against CRC, ii: to evaluate existing therapies alone or in combination with both immunomodulatory and standard chemotherapy.