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Consider the Intestinal Environment in Predicting Immunotherapy Response in Liver Cancer

By: Julia Fiederlein
Posted: Friday, September 30, 2022

Although the gut microbiota have been established as a prognostic factor and modulator of treatment sensitivity in patients with cancer who underwent immune checkpoint inhibition, data are limited for those with hepatocellular carcinoma. Thus, Francesca Romana Ponziani, MD, PhD, of Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, and colleagues conducted a study to evaluate the prognostic role of the gut microbiota and changes produced by immunotherapy on the intestinal environment in patients with cirrhosis and hepatocellular carcinoma. The results, which were published in Hepatology Communications, should prompt further studies in larger cohorts.

“Cirrhotic patients with hepatocellular carcinoma who respond to immune checkpoint inhibition appear to have a favorable composition of the gut microbiota and a low degree of intestinal inflammation,” the investigators remarked. “Dynamic fluctuations in the ratio between beneficial and harmful bacteria are related to changes in intestinal inflammation and permeability during treatment.”

A total of 11 patients who were treated with tremelimumab and/or durvalumab underwent gut microbiota profiling, quantification of fecal calprotectin, serum levels of zonulin-1, lipopolysaccharide binding protein, and PD-L1. The six patients who achieved disease control demonstrated lower median pretreatment fecal calprotectin (12.5 µg/g vs. 116.0 µg/g; P = .047) and PD-L1 serum (0.08 ng/mL vs. 1.04 ng.mL; P = .02) levels than nonresponders. According to the investigators, the relative abundance of Akkermansia was increased (adjusted P = .012) and that of Enterobacteriaceae was reduced (adjusted P = .04) in this group.

During treatment, fecal calprotectin demonstrated a temporal evolution opposite to the Akkermansia-to-Enterobacteriaceae ratio and gut microbiota alpha diversity; however, it was found to be similar to zonulin-1 and lipopolysaccharide binding protein. Bifidobacterium exhibited stable behavior in patients with a long follow-up, but Akkermansia seemed to be more variable. Akkermansia and Bifidobacterium demonstrated similar temporal patterns and causative relationships with Prevotella, Veillonella, Ruminococcus, Roseburia, Lachnospira, Faecalibacterium, and Clostridium.

Disclosure: The study authors reported no conflicts of interest.

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