Scientific Reports (May 2024)
Isobutyric acid enhances the anti-tumour effect of anti-PD-1 antibody
- Masakazu Murayama,
- Masahiro Hosonuma,
- Atsuo Kuramasu,
- Sei Kobayashi,
- Akiko Sasaki,
- Yuta Baba,
- Yoichiro Narikawa,
- Hitoshi Toyoda,
- Junya Isobe,
- Eiji Funayama,
- Kohei Tajima,
- Aya Sasaki,
- Yuki Maruyama,
- Yoshitaka Yamazaki,
- Midori Shida,
- Kazuyuki Hamada,
- Yuya Hirasawa,
- Toshiaki Tsurui,
- Hirotsugu Ariizumi,
- Tomoyuki Ishiguro,
- Risako Suzuki,
- Ryotaro Ohkuma,
- Yutaro Kubota,
- Atsushi Horiike,
- Takehiko Sambe,
- Mayumi Tsuji,
- Satoshi Wada,
- Shinichi Kobayashi,
- Toshikazu Shimane,
- Takuya Tsunoda,
- Hitome Kobayashi,
- Yuji Kiuchi,
- Kiyoshi Yoshimura
Affiliations
- Masakazu Murayama
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University
- Masahiro Hosonuma
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University
- Atsuo Kuramasu
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University
- Sei Kobayashi
- Department of Otorhinolaryngology, Fujigaoka Hospital
- Akiko Sasaki
- Division of Medical Pharmacology, Department of Pharmacology, Showa University School of Medicine
- Yuta Baba
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University
- Yoichiro Narikawa
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University
- Hitoshi Toyoda
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University
- Junya Isobe
- Department of Hospital Pharmaceutics, School of Pharmacy, Showa University
- Eiji Funayama
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University
- Kohei Tajima
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University
- Aya Sasaki
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University
- Yuki Maruyama
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University
- Yoshitaka Yamazaki
- Pharmacological Research Center, Showa University
- Midori Shida
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University
- Kazuyuki Hamada
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine
- Yuya Hirasawa
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine
- Toshiaki Tsurui
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University
- Hirotsugu Ariizumi
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine
- Tomoyuki Ishiguro
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine
- Risako Suzuki
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine
- Ryotaro Ohkuma
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine
- Yutaro Kubota
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine
- Atsushi Horiike
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine
- Takehiko Sambe
- Division of Clinical Pharmacology, Department of Pharmacology, Showa University School of Medicine
- Mayumi Tsuji
- Pharmacological Research Center, Showa University
- Satoshi Wada
- Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University
- Shinichi Kobayashi
- Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University
- Toshikazu Shimane
- Head and Neck Oncology Center, Showa University
- Takuya Tsunoda
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine
- Hitome Kobayashi
- Department of Otorhinolaryngology-Head and Neck Surgery, Showa University School of Medicine
- Yuji Kiuchi
- Division of Medical Pharmacology, Department of Pharmacology, Showa University School of Medicine
- Kiyoshi Yoshimura
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University
- DOI
- https://doi.org/10.1038/s41598-024-59677-1
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 10
Abstract
Abstract The low response rate of immune checkpoint inhibitors (ICIs) is a challenge. The efficacy of ICIs is influenced by the tumour microenvironment, which is controlled by the gut microbiota. In particular, intestinal bacteria and their metabolites, such as short chain fatty acids (SCFAs), are important regulators of cancer immunity; however, our knowledge on the effects of individual SCFAs remains limited. Here, we show that isobutyric acid has the strongest effect among SCFAs on both immune activity and tumour growth. In vitro, cancer cell numbers were suppressed by approximately 75% in humans and mice compared with those in controls. Oral administration of isobutyric acid to carcinoma-bearing mice enhanced the effect of anti-PD-1 immunotherapy, reducing tumour volume by approximately 80% and 60% compared with those in the control group and anti-PD-1 antibody alone group, respectively. Taken together, these findings may support the development of novel cancer therapies that can improve the response rate to ICIs.
