Isobutyric acid enhances the anti-tumour effect of anti-PD-1 antibody.

Autor: Murayama M; Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo, 157-8577, Japan.; Division of Medical Pharmacology, Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan.; Pharmacological Research Center, Showa University, Tokyo, Japan.; Department of Otorhinolaryngology-Head and Neck Surgery, Showa University School of Medicine, Tokyo, Japan., Hosonuma M; Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo, 157-8577, Japan.; Division of Medical Pharmacology, Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan.; Pharmacological Research Center, Showa University, Tokyo, Japan.; Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan., Kuramasu A; Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo, 157-8577, Japan., Kobayashi S; Department of Otorhinolaryngology, Fujigaoka Hospital, Yokohama, Japan., Sasaki A; Division of Medical Pharmacology, Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan.; Pharmacological Research Center, Showa University, Tokyo, Japan., Baba Y; Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo, 157-8577, Japan., Narikawa Y; Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo, 157-8577, Japan.; Division of Medical Pharmacology, Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan.; Pharmacological Research Center, Showa University, Tokyo, Japan.; Department of Otorhinolaryngology-Head and Neck Surgery, Showa University School of Medicine, Tokyo, Japan., Toyoda H; Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo, 157-8577, Japan.; Division of Medical Pharmacology, Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan.; Pharmacological Research Center, Showa University, Tokyo, Japan.; Department of Orthopaedic Surgery, School of Medicine, Showa University, Tokyo, Japan., Isobe J; Department of Hospital Pharmaceutics, School of Pharmacy, Showa University, Tokyo, Japan., Funayama E; Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo, 157-8577, Japan.; Pharmacological Research Center, Showa University, Tokyo, Japan.; Division of Pharmacology, Department of Pharmacology, Toxicology and Therapeutics, School of Pharmacy, Showa University, Tokyo, Japan., Tajima K; Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo, 157-8577, Japan., Sasaki A; Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo, 157-8577, Japan.; Division of Medical Pharmacology, Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan.; Pharmacological Research Center, Showa University, Tokyo, Japan., Maruyama Y; Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo, 157-8577, Japan.; Division of Medical Pharmacology, Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan.; Pharmacological Research Center, Showa University, Tokyo, Japan., Yamazaki Y; Pharmacological Research Center, Showa University, Tokyo, Japan.; Division of Toxicology, Department of Pharmacology, Toxicology and Therapeutics, Showa University School of Pharmacy, Tokyo, Japan., Shida M; Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo, 157-8577, Japan., Hamada K; Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan., Hirasawa Y; Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan., Tsurui T; Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo, 157-8577, Japan.; Division of Medical Pharmacology, Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan.; Pharmacological Research Center, Showa University, Tokyo, Japan.; Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan., Ariizumi H; Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan., Ishiguro T; Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan., Suzuki R; Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan., Ohkuma R; Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan., Kubota Y; Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan., Horiike A; Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan., Sambe T; Division of Clinical Pharmacology, Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan., Tsuji M; Pharmacological Research Center, Showa University, Tokyo, Japan., Wada S; Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan., Kobayashi S; Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan., Shimane T; Head and Neck Oncology Center, Showa University, Tokyo, Japan., Tsunoda T; Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan., Kobayashi H; Department of Otorhinolaryngology-Head and Neck Surgery, Showa University School of Medicine, Tokyo, Japan., Kiuchi Y; Division of Medical Pharmacology, Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan.; Pharmacological Research Center, Showa University, Tokyo, Japan., Yoshimura K; Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11, Kitakarasuyama, Setagaya-ku, Tokyo, 157-8577, Japan. kyoshim1@med.showa-u.ac.jp.; Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. kyoshim1@med.showa-u.ac.jp.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 May 17; Vol. 14 (1), pp. 11325. Date of Electronic Publication: 2024 May 17.
DOI: 10.1038/s41598-024-59677-1
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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