Clinical impact of probiotics on the efficacy of <scp>anti‐PD</scp>‐1 monotherapy in patients with nonsmall cell lung cancer: A multicenter retrospective survival analysis study with inverse probability of treatment weighting

Takada, Kazuki; Shimokawa, Mototsugu; Takamori, Shinkichi; Shimamatsu, Shinichiro; Hirai, Fumihiko; Tagawa, Tetsuzo; Okamoto, Tatsuro; Hamatake, Motoharu; Tsuchiya‐Kawano, Yuko; Otsubo, Kenji; Inoue, Koji; Yoneshima, Yasuto; Tanaka, Kentaro; Shibahara, Daisuke; Nakanishi, Yoichi; Mori, Masaki

doi:10.1002/ijc.33557

Cited by 48 publications

(45 citation statements)

References 48 publications

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“…Recent preliminary results of clinical studies have shown the ability of live biotherapeutic bacterium to induce compositional shifts in the gut microbiome and to provide the positive impact on the clinical benefit to ICB. 4 , 20 , 22 , 42 However, the impact of CBM588 on gut microbiota in patients with thoracic cancer had remained unknown. In the current study, we found patients who received CBM588 had a lesser abundance of potentially harmful oral-related bacterial genera, Atopobium and Streptococcus , 26 , 27 suggesting that CBM588 may have the potential to shift the gut dysbiosis to a favorable microbiota.…”

Section: Discussionmentioning

confidence: 99%

Clostridium butyricum therapy restores the decreased efficacy of immune checkpoint blockade in lung cancer patients receiving proton pump inhibitors

et al. 2022

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Oral microbiota is associated with human diseases including cancer. Emerging evidence suggests that proton pump inhibitors (PPIs), which allow the oral microbiome to translocate into the gut, negatively influence the efficacy of immune checkpoint blockade (ICB) in cancer patients. However, currently there is no effective treatment that restores the decreased efficacy. To address this issue, we retrospectively evaluated 118 advanced or recurrent non-small cell lung cancer (NSCLC) patients treated with ICB and analyzed 80 fecal samples of patients with lung cancer by 16S metagenomic sequencing. Clostridium butyricum therapy using C. butyricum MIYAIRI 588 (CBM588), a live biotherapeutic bacterial strain, was shown to improve the ICB efficacy in lung cancer. Thus, we investigated how CBM588 affects the efficacy of ICB and the gut microbiota of lung cancer patients undergoing PPI treatment. We found that PPI treatment significantly decreased the efficacy of ICB in NSCLC patients, however, CBM588 significantly restored the diminished efficacy of ICB and improved survival. In addition, CBM588 prolonged overall survival in patients receiving PPIs and antibiotics together. The fecal analysis revealed that PPI users had higher abundance of harmful oral-related pathobionts and lower abundance of beneficial gut bacteria for immunotherapy. In contrast, patients who received CBM588 had lesser relative abundance of potentially harmful oral-related bacteria in the gut. Our research suggests that manipulating commensal microbiota by CBM588 may improve the therapeutic efficacy of ICB in cancer patients receiving PPIs, highlighting the potential of oral-related microbiota in the gut as a new therapeutic target for cancer immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Clostridium butyricum therapy restores the decreased efficacy of immune checkpoint blockade in lung cancer patients receiving proton pump inhibitors

et al. 2022

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“…A multicenter and retrospective study conducted by Takada K et al has demonstrated that probiotics are linked to beneficial clinical outcomes in patients with advanced or recurrent NSCLC treated with anti-PD-1 monotherapy [ 120 ]. However, another study has reported paradoxical results in melanoma patients who took probiotic supplements while receiving immunotherapy and had a worse survival outcome.…”

Section: Gut Microbiota and Response To Systemic Therapy Including Im...mentioning

confidence: 99%

The Effect of the Gut Microbiota on Systemic and Anti-Tumor Immunity and Response to Systemic Therapy against Cancer

Aghamajidi

Vareki

2022

Cancers

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Gut microbiota can have opposing functions from pro-tumorigenic to anti-tumorigenic effects. Increasing preclinical and clinical evidence suggests that the intestinal microbiota affects cancer patients’ response to immune checkpoint inhibitors (ICIs) immunotherapy, such as anti-programmed cell death protein 1 (PD-1) and its ligand (PD-L1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Microbiota-induced inflammation possibly contributes to tumor growth and cancer development. Microbiota-derived metabolites can also be converted to carcinogenic agents related to genetic mutations and DNA damage in organs such as the colon. However, other attributes of microbiota, such as greater diversity and specific bacterial species and their metabolites, are linked to better clinical outcomes and potentially improved anti-tumor immunity. In addition, the intratumoral microbial composition strongly affects T-cell-mediated cytotoxicity and anti-tumor immune surveillance, adding more complexity to the cancer-microbiome-immune axis. Despite the emerging clinical evidence for the activity of the gut microbiota in immuno-oncology, the fundamental mechanisms of such activity are not well understood. This review provides an overview of underlying mechanisms by which the gut microbiota and its metabolites enhance or suppress anti-tumor immune responses. Understanding such mechanisms allows for better design of microbiome-specific treatment strategies to improve the clinical outcome in cancer patients undergoing systemic therapy.

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“…Clinically, Toi et al discovered that Lactobacillus casei strain Shirota consumption showed a negative correlation with breast cancer incidence (OR = 0.65, p = 0.048) [ 299 ]. Takada et al demonstrated that supplementation with probiotics improved progression-free survival (HR = 1.73, p = 0.0229), disease control (OR = 0.51, p = 0.0004), and overall response (OR = 0.43, p < 0.0001) in NSCLC patients receiving anti-programmed cell death 1 protein (anti-PD-1) monotherapy [ 300 ]. Additionally, the use of probiotics decreased the incidence of metachronous gastric cancer after endoscopic resection (HR = 0.29, p = 0.034) [ 301 ].…”

Section: Emerging Approaches: Interventions In the Gut Microbiota In ...mentioning

confidence: 99%

Common Pathogenetic Mechanisms Underlying Aging and Tumor and Means of Interventions

Shen¹,

He²,

Hou³

et al. 2022

Aging and disease

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Recently, there has been an increase in the incidence of malignant tumors among the older population. Moreover, there is an association between aging and cancer. During the process of senescence, the human body suffers from a series of imbalances, which have been shown to further accelerate aging, trigger tumorigenesis, and facilitate cancer progression. Therefore, exploring the junctions of aging and cancer and searching for novel methods to restore the junctions is of great importance to intervene against aging-related cancers. In this review, we have identified the underlying pathogenetic mechanisms of aging-related cancers by comparing alterations in the human body caused by aging and the factors that trigger cancers. We found that the common mechanisms of aging and cancer include cellular senescence, alterations in proteostasis, microbiota disorders (decreased probiotics and increased pernicious bacteria), persistent chronic inflammation, extensive immunosenescence, inordinate energy metabolism, altered material metabolism, endocrine disorders, altered genetic expression, and epigenetic modification. Furthermore, we have proposed that aging and cancer have common means of intervention, including novel uses of common medicine (metformin, resveratrol, and rapamycin), dietary restriction, and artificial microbiota intervention or selectively replenishing scarce metabolites. In addition, we have summarized the research progress of each intervention and revealed their bidirectional effects on cancer progression to compare their reliability and feasibility. Therefore, the study findings provide vital information for advanced research studies on age-related cancers. However, there is a need for further optimization of the described methods and more suitable methods for complicated clinical practices. In conclusion, targeting aging may have potential therapeutic effects on aging-related cancers.

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Clinical impact of probiotics on the efficacy of anti‐PD‐1 monotherapy in patients with nonsmall cell lung cancer: A multicenter retrospective survival analysis study with inverse probability of treatment weighting

Cited by 48 publications

References 48 publications

Clostridium butyricum therapy restores the decreased efficacy of immune checkpoint blockade in lung cancer patients receiving proton pump inhibitors

Clostridium butyricum therapy restores the decreased efficacy of immune checkpoint blockade in lung cancer patients receiving proton pump inhibitors

The Effect of the Gut Microbiota on Systemic and Anti-Tumor Immunity and Response to Systemic Therapy against Cancer

Common Pathogenetic Mechanisms Underlying Aging and Tumor and Means of Interventions

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