BMI/PRISM Combined Seminar Series

Thursday March 26th

Room: GB06

Time: 11:30 am-12:30 pm

Presenter: Dr. Kristi Baker Associate Professor University of Alberta

"Unequal Impact: Specific forms of genetic instability drive antitumor immunity in colorectal cancer”

Colorectal cancers (CRCs) are notoriously refractory to immune-mediated destruction. Only the small minority with microsatellite instability (MSI) due to defective DNA mismatch repair (MMR) contain significant amounts of CD8+ tumor infiltrating lymphocytes and induce strong antitumor immunity. Although neoantigens are necessary for immune recognition, they are not sufficient. Instead, MMR-induced genetic instability generates a unique tumor microenvironment favoring the recruitment and activation of antitumor immune cells. Activation of Type I IFN signaling in the MMR CRC cells reprograms the functional capacity of T cells and macrophages recruited to the tumors, while metabolic adaptations foster competition for essential nutrients between cancer and immune cells. Notably, these changes are not due to random genetic damage but instead result from the generation of specific forms of cytosolic DNA of microsatellite and mitochondrial origin as a result of failed MMR. Understanding how MMR-induced instability promotes a tumor protective response has important consequences for optimizing the delivery of DNA-damaging chemo and radiotherapies as well as the development of novel immunotherapeutic strategies to improve CRC treatment.

 

Next BMI/PRISM Combined Seminar

Thursday April 2nd

 Presenter: Dr. Yan Zhou - VIDO USask

 

 

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