Frontiers in Immunology (May 2023)
Turicibacter and Acidaminococcus predict immune-related adverse events and efficacy of immune checkpoint inhibitor
- Kazuyuki Hamada,
- Kazuyuki Hamada,
- Junya Isobe,
- Kouya Hattori,
- Kouya Hattori,
- Masahiro Hosonuma,
- Masahiro Hosonuma,
- Masahiro Hosonuma,
- Masahiro Hosonuma,
- Yuta Baba,
- Masakazu Murayama,
- Masakazu Murayama,
- Masakazu Murayama,
- Masakazu Murayama,
- Yoichiro Narikawa,
- Yoichiro Narikawa,
- Yoichiro Narikawa,
- Yoichiro Narikawa,
- Hitoshi Toyoda,
- Hitoshi Toyoda,
- Hitoshi Toyoda,
- Hitoshi Toyoda,
- Eiji Funayama,
- Kohei Tajima,
- Kohei Tajima,
- Midori Shida,
- Yuya Hirasawa,
- Toshiaki Tsurui,
- Hirotsugu Ariizumi,
- Tomoyuki Ishiguro,
- Risako Suzuki,
- Ryotaro Ohkuma,
- Yutaro Kubota,
- Takehiko Sambe,
- Mayumi Tsuji,
- Mayumi Tsuji,
- Satoshi Wada,
- Yuji Kiuchi,
- Yuji Kiuchi,
- Shinichi Kobayashi,
- Atsuo Kuramasu,
- Atsushi Horiike,
- Yun-Gi Kim,
- Takuya Tsunoda,
- Kiyoshi Yoshimura,
- Kiyoshi Yoshimura
Affiliations
- Kazuyuki Hamada
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
- Kazuyuki Hamada
- Department of Chest Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan
- Junya Isobe
- Department of Hospital Pharmaceutics, School of Pharmacy, Showa University, Tokyo, Japan
- Kouya Hattori
- Research Center for Drug Discovery and Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, Japan
- Kouya Hattori
- Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, Japan
- Masahiro Hosonuma
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
- Masahiro Hosonuma
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan
- Masahiro Hosonuma
- Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan
- Masahiro Hosonuma
- Pharmacological Research Center, Showa University, Tokyo, Japan
- Yuta Baba
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan
- Masakazu Murayama
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan
- Masakazu Murayama
- Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan
- Masakazu Murayama
- Pharmacological Research Center, Showa University, Tokyo, Japan
- Masakazu Murayama
- Department of Otorhinolaryngology-Head and Neck Surgery, Showa University School of Medicine, Tokyo, Japan
- Yoichiro Narikawa
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan
- Yoichiro Narikawa
- Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan
- Yoichiro Narikawa
- Pharmacological Research Center, Showa University, Tokyo, Japan
- Yoichiro Narikawa
- Department of Otorhinolaryngology-Head and Neck Surgery, Showa University School of Medicine, Tokyo, Japan
- Hitoshi Toyoda
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan
- Hitoshi Toyoda
- Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan
- Hitoshi Toyoda
- Pharmacological Research Center, Showa University, Tokyo, Japan
- Hitoshi Toyoda
- 0Department of Orthopedic Surgery, School of Medicine, Showa University, Tokyo, Japan
- Eiji Funayama
- 1Division of Pharmacology, Department of Pharmacology, School of Pharmacy, Showa University, Tokyo, Japan
- Kohei Tajima
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan
- Kohei Tajima
- 2Department of Gastroenterological Surgery, Tokai University School of Medicine, Kanagawa, Japan
- Midori Shida
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan
- Yuya Hirasawa
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
- Toshiaki Tsurui
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
- Hirotsugu Ariizumi
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
- Tomoyuki Ishiguro
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
- Risako Suzuki
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
- Ryotaro Ohkuma
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
- Yutaro Kubota
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
- Takehiko Sambe
- 3Division of Clinical Pharmacology, Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan
- Mayumi Tsuji
- Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan
- Mayumi Tsuji
- Pharmacological Research Center, Showa University, Tokyo, Japan
- Satoshi Wada
- 4Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan
- Yuji Kiuchi
- Department of Pharmacology, Showa University School of Medicine, Tokyo, Japan
- Yuji Kiuchi
- Pharmacological Research Center, Showa University, Tokyo, Japan
- Shinichi Kobayashi
- 5Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan
- Atsuo Kuramasu
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan
- Atsushi Horiike
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
- Yun-Gi Kim
- Research Center for Drug Discovery and Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, Japan
- Takuya Tsunoda
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
- Kiyoshi Yoshimura
- Division of Medical Oncology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
- Kiyoshi Yoshimura
- Department of Clinical Immuno Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, Tokyo, Japan
- DOI
- https://doi.org/10.3389/fimmu.2023.1164724
- Journal volume & issue
-
Vol. 14
Abstract
IntroductionImmune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race. Gut microbiota composition in Japanese cancer patients and the efficacy of immunotherapy remain unknown. MethodsWe investigated the gut microbiota of 26 patients with solid tumors prior to immune checkpoint inhibitor monotherapy to identify bacteria involved in the efficacy of these drugs and immune-related adverse events (irAEs).ResultsThe genera Prevotella and Parabacteroides were relatively common in the group showing efficacy towards the anti-PD-1 antibody treatment (effective group). The proportions of Catenibacterium (P = 0.022) and Turicibacter (P = 0.049) were significantly higher in the effective group than in the ineffective group. In addition, the proportion of Desulfovibrion (P = 0.033) was significantly higher in the ineffective group. Next, they were divided into irAE and non-irAE groups. The proportions of Turicibacter (P = 0.001) and Acidaminococcus (P = 0.001) were significantly higher in the group with irAEs than in those without, while the proportions of Blautia (P = 0.013) and the unclassified Clostridiales (P = 0.027) were significantly higher in the group without irAEs than those with. Furthermore, within the Effective group, Acidaminococcus and Turicibacter (both P = 0.001) were more abundant in the subgroup with irAEs than in those without them. In contrast, Blautia (P = 0.021) and Bilophila (P= 0.033) were statistically significantly more common in those without irAEs.DiscussionOur Study suggests that the analysis of the gut microbiota may provide future predictive markers for the efficacy of cancer immunotherapy or the selection of candidates for fecal transplantation for cancer immunotherapy.
Keywords
- clinical efficacy
- gut microbiota
- immune checkpoint inhibitors
- immune-related adverse events
- PD-1 inhibitor
- Turicibacter
