The EACR’s ‘Highlights in Cancer Research’ is a regular summary of the most interesting and impactful recent papers in cancer research, curated by the Board of the European Association for Cancer Research (EACR).
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5. A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers
Fidelle, M., Rauber, C., Alves Costa Silva, C. et al. Science. 380 (6649): eabo2296 (2023).
doi: 10.1126/science.abo2296.
Summary of the findings
In Fidelle, Rauber & Alves Costa et al., we demonstrate a mechanistic link between antibiotics (ABX) and compromised cancer treatment effectiveness using programmed cell death protein 1 (PD-1) blockade. The study reveals that ABX can suppress the immune system by downregulating a gut-specific cell adhesion molecule called “mucosal addressin cell adhesion molecule 1 (MAdCAM-1)” in the ileum, leading to the emigration of suppressive immune cells away from the intestine into distant tumours, where they inhibit PD-1 antibody efficacy. These immunosuppressive T cells were characterized by a Treg/Th17 phenotype. Enterocloster species, which thrive after ABX use, were found responsible for triggering MAdCAM-1 suppression and migration of these suppressive immune cells. Faecal microbiota transplantation aimed at restoring gut microbiota eubiosis or interleukin-17A neutralization was shown to prevent ABX-induced immunosuppression. In cancer patients treated with PD-1 blockade, low serum levels of soluble MAdCAM-1 were associated with poor clinical outcomes (compared with normal levels) in lung, kidney, and bladder cancer patients, supporting the impact of the MAdCAM-1-α4β7 axis in cancer immunosurveillance.
The figure was kindly created by Stefan Homentcovschi.
Future impact
These findings shed light on the complex interactions between gut bacteria, antibiotics, and cancer immunotherapy. Serum soluble MAdCAM holds promise as a potential biomarker to identify patients at high risk of gut microbiota dysbiosis and PD-1 blockade treatment failure, paving the way to stratify patients for microbiota-centered interventions.
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The Cancer Researcher is an online magazine for the cancer research community from the European Association for Cancer Research.
The EACR, a registered charity, is a global community for those working and studying in cancer research. Our mission is “The advancement of cancer research for the public benefit: from basic research to prevention, treatment and care.”
Summary of the findings
Summary of the findings
