Mechanisms of Response to Immune Checkpoint Inhibitors in Microsatellite Stable Colorectal Cancer

At the 2023 World Congress on Gastrointestinal Cancers, Guillen Argiles, MD, Memorial Sloan Kettering Cancer Center, New York, New York, discussed the mechanisms of response and resistance to immune checkpoint inhibitors among patients with microsatellite stable, non-polyposis colorectal cancer.

This discussion highlights “mechanisms that make these tumors not respond to immunotherapy,” and preclinical evidence which may indicate “a microenvironment that specifically shuts down the immune response” in the case of liver metastases.

Transcript:

Hello, my name is Guillen Argiles, and I work at Memorial Sloan Kettering Cancer Center. At the 2023 World Congress on Gastrointestinal Cancers, I reviewed the topic of persistent mechanisms to immune checkpoint inhibitors in MSS [microsatellite stable], non-polyposis colorectal cancer.

During my talk I reviewed all the mechanisms that make these tumors not respond to immunotherapy. What we went through is the fact that the current panorama of therapy in cancer relies on the presentation of neo-antigens by the tumor cells. What we saw during the talk is that these tumors, they don't have enough neo-antigen quality and enough neo-antigen quantity, and this makes the tumors elusive to the immune system.

Also, we reviewed the main strategies used so far trying to synergize with immunotherapy and trying to lower the bar for neo-antigen requirements. Some of these strategies were more successful than the others and particularly we discussed the combination of tyrosine kinase inhibitors with anti-PD-1 agents and anti-CTLA4 agents with anti-PD-1s.

What we saw is that we've been facing trouble, even though that some patients are able to benefit from the therapy and get significant benefit. We reviewed which were the resistant mechanisms in this population: the presence of a liver metastasis. We reviewed the biological insights that makes the liver disease not respond to these therapies and we reviewed the preclinical evidence that says that maybe there's a microenvironment that specifically shuts down the immune response in this territory and also, we talked about possible solutions for the future. Thank you so much.

Source:

Argiles G. Resistance factors to IOs. Presented at the 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain.