Association of <i>Clostridium butyricum</i> Therapy Using the Live Bacterial Product CBM588 with the Survival of Patients with Lung Cancer Receiving Chemoimmunotherapy Combinations

Yusuke Tomita; Shinya Sakata; Kosuke Imamura; Shinji Iyama; Takayuki Jodai; Koichi Saruwatari; Shohei Hamada; Kimitaka Akaike; Moriyasu Anai; Kazuaki Fukusima; Akira Takaki; Hirotake Tsukamoto; Yoshihiko Goto; Chihiro Motozono; Kenji Sugata; Yorifumi Satou; Takamasa Ueno; Tokunori Ikeda; Takuro Sakagami

doi:10.3390/cancers16010047

Cancers (Dec 2023)

Association of <i>Clostridium butyricum</i> Therapy Using the Live Bacterial Product CBM588 with the Survival of Patients with Lung Cancer Receiving Chemoimmunotherapy Combinations

Yusuke Tomita,
Shinya Sakata,
Kosuke Imamura,
Shinji Iyama,
Takayuki Jodai,
Koichi Saruwatari,
Shohei Hamada,
Kimitaka Akaike,
Moriyasu Anai,
Kazuaki Fukusima,
Akira Takaki,
Hirotake Tsukamoto,
Yoshihiko Goto,
Chihiro Motozono,
Kenji Sugata,
Yorifumi Satou,
Takamasa Ueno,
Tokunori Ikeda,
Takuro Sakagami

Affiliations

Yusuke Tomita: Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan
Shinya Sakata: Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan
Kosuke Imamura: Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan
Shinji Iyama: Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan
Takayuki Jodai: Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan
Koichi Saruwatari: Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan
Shohei Hamada: Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan
Kimitaka Akaike: Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan
Moriyasu Anai: Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan
Kazuaki Fukusima: Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan
Akira Takaki: Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan
Hirotake Tsukamoto: Division of Clinical Immunology and Cancer Immunotherapy, Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
Yoshihiko Goto: Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan
Chihiro Motozono: Division of Infection and Immunity, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Honjo 2-1-1, Chuo-ku, Kumamoto 860-0811, Japan
Kenji Sugata: Division of Genomics and Transcriptomics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan
Yorifumi Satou: Division of Genomics and Transcriptomics, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan
Takamasa Ueno: Division of Infection and Immunity, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Honjo 2-1-1, Chuo-ku, Kumamoto 860-0811, Japan
Tokunori Ikeda: Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan
Takuro Sakagami: Department of Respiratory Medicine, Kumamoto University Hospital, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan

DOI: https://doi.org/10.3390/cancers16010047
Journal volume & issue: Vol. 16, no. 1
p. 47

Abstract

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The gut microbiota has emerged as a key regulator of immune checkpoint inhibitor (ICI) efficacy. Therapeutic approaches aimed at manipulating the microbiota through targeted reconstitution to enhance cancer treatment outcomes have garnered considerable attention. A single live microbial biotherapeutic bacterium, Clostridium butyricum MIYAIRI 588 strain (CBM588), has been shown to enhance the effects of ICI monotherapy in patients with advanced lung cancer. However, whether CBM588 affects the outcomes of chemoimmunotherapy combinations in lung cancer remains unknown. We hypothesized that CBM588 augments the effect of chemoimmunotherapy combinations and restores diminished effectiveness in patients with non-small cell lung cancer (NSCLC) receiving dysbiosis-inducing drugs. To validate this hypothesis, we retrospectively analyzed 106 patients with stage IV or recurrent metastatic NSCLC consecutively treated with chemoimmunotherapy combinations. A survival analysis was performed employing univariate and multivariate Cox proportional hazard models with inverse probability of treatment weighting (IPTW) using propensity scores. Forty-five percent of patients received Clostridium butyricum therapy. CBM588 significantly extended overall survival in patients with NSCLC receiving chemoimmunotherapy. The favorable impact of CBM588 on the efficacy of chemoimmunotherapy combinations varied based on tumor-programmed cell death ligand 1 (PD-L1) expression. The survival benefit of CBM588 in the PD-L1 <1% cohort was higher than that in the PD-L1 1–49% and PD-L1 ≥ 50% cohorts. Furthermore, CBM588 was associated with improved overall survival in patients receiving proton pump inhibitors and/or antibiotics. CBM588-induced manipulation of the commensal microbiota holds the potential to enhance the efficacy of chemoimmunotherapy combinations, warranting further exploration of the synergy between CBM588 and immunotherapy.

Published in Cancers

ISSN: 2072-6694 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.mdpi.com/journal/cancers/

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