ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1528521
This article is part of the Research TopicMicrobiota-Immune Interactions: A New Frontier in Cancer Treatment OptimizationView all 7 articles
Veillonella and Streptococcus are associated with aging of the gut microbiota and affect the efficacy of immune checkpoint inhibitors
Provisionally accepted
Yuya Hirasawa1
Junya Isobe2
Masahiro Hosonuma1
Toshiaki Tsurui1
Yuta Baba3
Eiji Funayama3Kohei Tajima3Masakazu Murayama3
Yoichiro Narikawa3Hitoshi Toyoda3Midori Shida3Aya Sasaki3Yuuki Maruyama3Yasunobu Amari3Emiko Mura1
Risako Suzuki1Nana Iriguchi1Tomoyuki Ishiguro1
Ryotaro Ohkuma1
Masahiro Shimokawa1Hirotsugu Ariizumi1Yutaro Kubota1
Atsushi Horiike1
Takehiko Sambe3Naoki Uchida3
Satoshi Wada1Shinichi Kobayashi3
Yuji Kiuchi3
ATSUO KURAMASU3
Kiyoshi Yoshimura1*
Takuya Tsunoda1- 1School of Medicine, Showa University, Tokyo, Japan
- 2Department of Hospital Pharmaceutics, School of Pharmacy, Showa University, Tokyo, Japan
- 3Showa University, Shinagawa, Japan
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Introduction: The rapid increase in the number of elderly patients with cancer necessitates treatment strategies based on the effects of aging because of drastic side effects of cytotoxic anticancer agents. Immune checkpoint inhibitors (ICIs) are relatively less toxic and can be easily administered to vulnerable and aged patients suffering from cancer. The diversity of gut microbiota and specific bacteria affects the efficacy and safety of ICIs. Therefore, this study aimed to assess the effect of aging on gut microbiota that play crucial roles in determining antitumor efficacy of drugs. Methods: Stool samples were collected from 36 aged patients pathologically diagnosed with solid tumors before the start of drug therapy, and gut microbial composition was analyzed using next generation sequencing. The association between gut microbiota and efficacy and safety of ICIs was analyzed. Results: The abundance of Veillonella species significantly decreased in patients aged ≥75 years. Additionally, the gut microbiota in the responder group was significantly higher than that in the nonresponder group regardless of age. The abundance of Streptococcus species was significantly higher in the responder group than that in the non-responder group. Conclusions: These gut microbiota changes with aging, and its characteristics are important parameters that also affect the efficacy of ICIs.
Keywords: Gut Microbiota, Immune checkpoint inhibitor, Aging, Veillonella, Streptococcus
Received: 15 Nov 2024; Accepted: 22 Apr 2025.
Copyright: © 2025 Hirasawa, Isobe, Hosonuma, Tsurui, Baba, Funayama, Tajima, Murayama, Narikawa, Toyoda, Shida, Sasaki, Maruyama, Amari, Mura, Suzuki, Iriguchi, Ishiguro, Ohkuma, Shimokawa, Ariizumi, Kubota, Horiike, Sambe, Uchida, Wada, Kobayashi, Kiuchi, KURAMASU, Yoshimura and Tsunoda. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kiyoshi Yoshimura, School of Medicine, Showa University, Tokyo, Japan
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.