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

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

Pei-Jung Lee  1 , Chien-Min Hung  1 , Ai-Jen Yang  1 , Cheng-Yu Hou  1 , Hung-Wen Chou  2 , Yi-Chung Chang  3 , Wen-Cheng Chu  1 , Wen-Yen Huang  1 , Wen-Chih Kuo  1 , Chia-Chun Yang  3 , Kuo-I Lin  4 , Kuo-Hsuan Hung  4 , Li-Chun Chang  5 , Kang-Yun Lee  6 , Han-Pin Kuo  7   8 , Kung-Ming Lu  9 , Hsin-Chih Lai  10 , Ming-Liang Kuo  9 , Wan-Jiun Chen  1
Affiliations

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

Pei-Jung Lee et al. Gut Microbes. 2024 Jan-Dec.

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.

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Conflict of interest statement

The authors declare the following potential conflicts of interest: PJL, CMH, AJY, CYH, WCC, WYH, WCK, KML, MLK and WJC are employed by Microbio Co., Ltd.; YCC and CCY are employed by Microbio (Shanghai) Biotech Company; HWC is employed by Oneness Biotech; and HCL is employed by Revivebio Co., Ltd.

Figures

Figure 1.
Figure 1.
MS-20 plus an anti-PD1 antibody inhibited colon cancer growth in vivo.
Figure 2.
Figure 2.
MS-20-treated feces enhanced the efficacy of the anti-PD1 antibody.
Figure 3.
Figure 3.
MS-20 distinctly modulated the gut microbiota associated with tumor reduction and CD8+ T-cell infiltration.
Figure 4.
Figure 4.
Intestinal immunity was enriched after MS-20 treatment.
Figure 5A.
Figure 5A.
MS-20 regulated the microbiota of cancer patients ex vivo.
Figure 5B.
Figure 5B.
continued.
Figure 6.
Figure 6.
Proposed mechanism of the effect of MS-20.
See this image and copyright information in PMC

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