breakthrough board scholar

Investigating the Mechanisms and Therapeutic Use of Commensal Microbes in Cancer Immunotherapy

While immune checkpoint inhibitors (ICIs), a type of immunotherapy, have revolutionized cancer therapy, a significant proportion of patients do not respond to these treatments. It is becoming increasingly evident that gut commensal microbes play a crucial role in regulating the efficacy of ICIs.  However, scientists face significant challenges in understanding how, due to our limited knowledge of the underlying mechanisms essential for developing effective immunotherapies that leverage the gut microbiome.  Dr. Park has recently demonstrated that a specific gut microbe called Coprobacillus cateniformis enhances immunotherapy by downregulating a particular novel immune pathway. Moreover, targeting this pathway overcomes microbiome-related resistance to cancer immunotherapy.  With his Young Investigator Award, Dr. Park will seek to explain the exact mechanism by which gut-resident microbes influence this immune pathway and the tumor microenvironment.

Dr. Park’s preliminary data suggests that specific gut bacteria molecules  directly signal to innate immune receptors, leading to substantial changes in the macrophages within the tumor microenvironment. This project will use gnotobiotic tumor models and genetic manipulation to examine the signaling mechanisms gut microbes use to make changes in the immune environment to promote anti-tumor immunity.  Dr. Park will also investigate the role of commensal microbe-induced inflammation in the tumor microenvironment.  Armed with these findings, he will test the use of bacterial molecules to enhance the efficacy of ICIs.  Dr. Park hopes to provide critical insights into  how  the  gut  microbiota  regulates  anti-tumor immunity and inform new therapeutic strategies for patients who do not respond to PD-1 pathway blockade.