Association of Clostridium butyricum Therapy Using the Live Bacterial Product CBM588 with the Survival of Patients with Lung Cancer Receiving Chemoimmunotherapy Combinations
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 biotherapeut...
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| Veröffentlicht in: | Cancers 2023-12, Vol.16 (1), p.47 |
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| creator | Tomita, Yusuke Sakata, Shinya Imamura, Kosuke Iyama, Shinji Jodai, Takayuki Saruwatari, Koichi Hamada, Shohei Akaike, Kimitaka Anai, Moriyasu Fukusima, Kazuaki Takaki, Akira Tsukamoto, Hirotake Goto, Yoshihiko Motozono, Chihiro Sugata, Kenji Satou, Yorifumi Ueno, Takamasa Ikeda, Tokunori Sakagami, Takuro |
| description | 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,
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
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 |
| doi_str_mv | 10.3390/cancers16010047 |
| format | Article |
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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
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.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers16010047</identifier><identifier>PMID: 38201474</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antibiotics ; Apoptosis ; Cancer therapies ; Cell death ; Chemotherapy ; Clinical outcomes ; Clostridium butyricum ; Dysbacteriosis ; Histology ; Immune checkpoint inhibitors ; Immunosuppressive agents ; Immunotherapy ; Intestinal microflora ; Lung cancer ; Medical records ; Metastases ; Metastasis ; Microbiota ; Non-small cell lung carcinoma ; Patients ; PD-L1 protein ; Proton pump inhibitors ; Small cell lung carcinoma ; Survival analysis ; Tumors</subject><ispartof>Cancers, 2023-12, Vol.16 (1), p.47</ispartof><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-67e918654fd8a9f400863595fca11609b40d27729e38a0d7fbaba75d4e4790483</citedby><cites>FETCH-LOGICAL-c422t-67e918654fd8a9f400863595fca11609b40d27729e38a0d7fbaba75d4e4790483</cites><orcidid>0000-0002-1495-7810 ; 0000-0002-5520-3185 ; 0000-0003-4852-4236 ; 0000-0002-9680-7559 ; 0000-0003-3214-1652</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10778075/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10778075/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38201474$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tomita, Yusuke</creatorcontrib><creatorcontrib>Sakata, Shinya</creatorcontrib><creatorcontrib>Imamura, Kosuke</creatorcontrib><creatorcontrib>Iyama, Shinji</creatorcontrib><creatorcontrib>Jodai, Takayuki</creatorcontrib><creatorcontrib>Saruwatari, Koichi</creatorcontrib><creatorcontrib>Hamada, Shohei</creatorcontrib><creatorcontrib>Akaike, Kimitaka</creatorcontrib><creatorcontrib>Anai, Moriyasu</creatorcontrib><creatorcontrib>Fukusima, Kazuaki</creatorcontrib><creatorcontrib>Takaki, Akira</creatorcontrib><creatorcontrib>Tsukamoto, Hirotake</creatorcontrib><creatorcontrib>Goto, Yoshihiko</creatorcontrib><creatorcontrib>Motozono, Chihiro</creatorcontrib><creatorcontrib>Sugata, Kenji</creatorcontrib><creatorcontrib>Satou, Yorifumi</creatorcontrib><creatorcontrib>Ueno, Takamasa</creatorcontrib><creatorcontrib>Ikeda, Tokunori</creatorcontrib><creatorcontrib>Sakagami, Takuro</creatorcontrib><title>Association of Clostridium butyricum Therapy Using the Live Bacterial Product CBM588 with the Survival of Patients with Lung Cancer Receiving Chemoimmunotherapy Combinations</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>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,
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
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.</description><subject>Antibiotics</subject><subject>Apoptosis</subject><subject>Cancer therapies</subject><subject>Cell death</subject><subject>Chemotherapy</subject><subject>Clinical outcomes</subject><subject>Clostridium butyricum</subject><subject>Dysbacteriosis</subject><subject>Histology</subject><subject>Immune checkpoint inhibitors</subject><subject>Immunosuppressive agents</subject><subject>Immunotherapy</subject><subject>Intestinal microflora</subject><subject>Lung cancer</subject><subject>Medical records</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Microbiota</subject><subject>Non-small cell lung carcinoma</subject><subject>Patients</subject><subject>PD-L1 protein</subject><subject>Proton pump inhibitors</subject><subject>Small cell 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of Clostridium butyricum Therapy Using the Live Bacterial Product CBM588 with the Survival of Patients with Lung Cancer Receiving Chemoimmunotherapy Combinations</title><author>Tomita, Yusuke ; Sakata, Shinya ; Imamura, Kosuke ; Iyama, Shinji ; Jodai, Takayuki ; Saruwatari, Koichi ; Hamada, Shohei ; Akaike, Kimitaka ; Anai, Moriyasu ; Fukusima, Kazuaki ; Takaki, Akira ; Tsukamoto, Hirotake ; Goto, Yoshihiko ; Motozono, Chihiro ; Sugata, Kenji ; Satou, Yorifumi ; Ueno, Takamasa ; Ikeda, Tokunori ; Sakagami, Takuro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-67e918654fd8a9f400863595fca11609b40d27729e38a0d7fbaba75d4e4790483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Antibiotics</topic><topic>Apoptosis</topic><topic>Cancer therapies</topic><topic>Cell death</topic><topic>Chemotherapy</topic><topic>Clinical outcomes</topic><topic>Clostridium butyricum</topic><topic>Dysbacteriosis</topic><topic>Histology</topic><topic>Immune checkpoint inhibitors</topic><topic>Immunosuppressive agents</topic><topic>Immunotherapy</topic><topic>Intestinal microflora</topic><topic>Lung cancer</topic><topic>Medical records</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Microbiota</topic><topic>Non-small cell lung carcinoma</topic><topic>Patients</topic><topic>PD-L1 protein</topic><topic>Proton pump inhibitors</topic><topic>Small cell lung carcinoma</topic><topic>Survival analysis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tomita, Yusuke</creatorcontrib><creatorcontrib>Sakata, Shinya</creatorcontrib><creatorcontrib>Imamura, Kosuke</creatorcontrib><creatorcontrib>Iyama, Shinji</creatorcontrib><creatorcontrib>Jodai, Takayuki</creatorcontrib><creatorcontrib>Saruwatari, Koichi</creatorcontrib><creatorcontrib>Hamada, Shohei</creatorcontrib><creatorcontrib>Akaike, 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of Clostridium butyricum Therapy Using the Live Bacterial Product CBM588 with the Survival of Patients with Lung Cancer Receiving Chemoimmunotherapy Combinations</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2023-12-21</date><risdate>2023</risdate><volume>16</volume><issue>1</issue><spage>47</spage><pages>47-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>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,
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
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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>38201474</pmid><doi>10.3390/cancers16010047</doi><orcidid>https://orcid.org/0000-0002-1495-7810</orcidid><orcidid>https://orcid.org/0000-0002-5520-3185</orcidid><orcidid>https://orcid.org/0000-0003-4852-4236</orcidid><orcidid>https://orcid.org/0000-0002-9680-7559</orcidid><orcidid>https://orcid.org/0000-0003-3214-1652</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancers, 2023-12, Vol.16 (1), p.47 |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Antibiotics Apoptosis Cancer therapies Cell death Chemotherapy Clinical outcomes Clostridium butyricum Dysbacteriosis Histology Immune checkpoint inhibitors Immunosuppressive agents Immunotherapy Intestinal microflora Lung cancer Medical records Metastases Metastasis Microbiota Non-small cell lung carcinoma Patients PD-L1 protein Proton pump inhibitors Small cell lung carcinoma Survival analysis Tumors |
| title | Association of Clostridium butyricum Therapy Using the Live Bacterial Product CBM588 with the Survival of Patients with Lung Cancer Receiving Chemoimmunotherapy Combinations |
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