MS-20 enhances the gut microbiota-associated antitumor effects of anti-PD1 antibody

Gut Microbes. 2024 Jan-Dec;16(1):2380061. doi: 10.1080/19490976.2024.2380061. Epub 2024 Jul 30.

Abstract

Cancer immunotherapy has been regarded as a promising strategy for cancer therapy by blocking immune checkpoints and evoking immunity to fight cancer, but its efficacy seems to be heterogeneous among patients. Manipulating the gut microbiota is a potential strategy for enhancing the efficacy of immunotherapy. Here, we report that MS-20, also known as "Symbiota®", a postbiotic that comprises abundant microbial metabolites generated from a soybean-based medium fermented with multiple strains of probiotics and yeast, inhibited colon and lung cancer growth in combination with an anti-programmed cell death 1 (PD1) antibody in xenograft mouse models. Mechanistically, MS-20 remodeled the immunological tumor microenvironment by increasing effector CD8+ T cells and downregulating PD1 expression, which were mediated by the gut microbiota. Fecal microbiota transplantation (FMT) from mice receiving MS-20 treatment to recipient mice increased CD8+ T-cell infiltration into the tumor microenvironment and significantly improved antitumor activity when combined with anti-PD1 therapy. Notably, the abundance of Ruminococcus bromii, which increased following MS-20 treatment, was positively associated with a reduced tumor burden and CD8+ T-cell infiltration in vivo. Furthermore, an ex vivo study revealed that MS-20 could alter the composition of the microbiota in cancer patients, resulting in distinct metabolic pathways associated with favorable responses to immunotherapy. Overall, MS-20 could act as a promising adjuvant agent for enhancing the efficacy of immune checkpoint-mediated antitumor therapy.

Keywords: Gut microbiota; cancer immunotherapy; colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes* / immunology
  • Cell Line, Tumor
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / microbiology
  • Colonic Neoplasms / therapy
  • Fecal Microbiota Transplantation
  • Female
  • Gastrointestinal Microbiome*
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immunotherapy
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / immunology
  • Lung Neoplasms / therapy
  • Mice
  • Mice, Inbred BALB C
  • Probiotics / administration & dosage
  • Probiotics / pharmacology
  • Programmed Cell Death 1 Receptor* / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor* / immunology
  • Programmed Cell Death 1 Receptor* / metabolism
  • Tumor Microenvironment* / immunology
  • Xenograft Model Antitumor Assays

Substances

  • Programmed Cell Death 1 Receptor
  • Immune Checkpoint Inhibitors

Grants and funding

This study was financially supported by Microbio Co., Ltd.