Interaction of bacterial genera associated with therapeutic response to immune checkpoint PD-1 blockade in a United States cohort

The functional relationship between immunity, intestinal microbiota and non-small cell lung cancer (NSCLC) response to immune checkpoint inhibitors (ICI) PD1 in an American cohort remains unexplored. In a new Genome Medicine study titled, “Interaction of bacterial genera associated with therapeutic response to immune checkpoint PD-1 blockade in a United States cohort,” Christian Jobin, Ph.D., co-leader of the Cancer Center’s Cancer Therapeutics and Host Response research program, PhD student Rachel Newsome and Raad Gharaibeh Ph.D., microbial genomic expert, ( Jobin Research Lab team),  explore this unknown. This study was financed through an FACCA grant and the cohort was assembled at Moffitt Cancer Center.

“The study points to the existence of bacteria that could be coupled with therapeutics to enhance patient’s responsiveness to immunotherapy,” said Dr. Jobin.

Christian Jobin, Ph.D.

In the study, fecal microbiota DNA was sequenced from 65 fecal biospecimens obtained from patients with NSCLC treated with PD-1.  The study revealed that microbiota composition was significantly different between responders and non-responders at baseline before PD-1 exposure but not after treatment. Colonization of Lewis lung carcinoma bearing mice with preserved microbiota from patients with lung cancer, responders and non-responders, resulted in improved response to PD1 only in mice colonized with bacteria from responders.

A beneficial microbiota network in responder patients included the genera Colidextribacter, Frisingicoccus, Marvinbryantia and Blautia. The role of isolate-specific function and bacterial gene expression in gut microbial-driven responsiveness to ICI has been underappreciated. This work supports further investigation using isolate-driven models to characterize the mechanisms underlying this phenomenon.

The Jobin’s group is currently “mining” the intestinal microbiota of responder patients to isolate and characterize bacteria that could be used to improve drug efficacy in patients with NSCLC.

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