Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy

Author:

Griffin Matthew E.123ORCID,Espinosa Juliel1ORCID,Becker Jessica L.1,Luo Ji-Dung3ORCID,Carroll Thomas S.3,Jha Jyoti K.4ORCID,Fanger Gary R.4ORCID,Hang Howard C.12ORCID

Affiliation:

1. Laboratory of Chemical Biology and Microbial Pathogenesis, The Rockefeller University, 1230 York Ave., New York, NY 10065, USA.

2. Departments of Immunology and Microbiology and Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

3. Bioinformatics Resource Center, The Rockefeller University, 1230 York Ave., New York, NY 10065, USA.

4. Rise Therapeutics, 1405 Research Blvd. Suite 220, Rockville, MD 20850, USA.

Abstract

SagA promotes immunotherapy response The gut microbiome can influence the treatment outcome for cancer patients receiving PD-L1 immunotherapy, but the mechanisms underlying favorable responses are unclear. Griffin et al . found that a particular type of bacteria called enterococci enhance anti–PD-L1 immunotherapy in mice (see the Perspective by Ansaldo and Belkaid). The researchers show that enterococci secrete an enzyme called SagA that breaks down components of the bacterial cell wall. This process results in the release of muramyl peptide fragments, which in turn act as stimulatory molecules to promote signaling of the innate immune sensor protein NOD2 and improved immunotherapy responses. —PNK

Funder

National Institutes of Health

Melanoma Research Foundation

ASCRS Research Foundation

Hope Funds for Cancer Research

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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