The role of the gut microbiome on the efficacy of immune checkpoint inhibitors in Japanese responder patients with advanced non-small cell lung cancer

Katayama, Yuki; Yamada, Tadaaki; Shimamoto, Takayuki; Iwasaku, Masahiro; Kaneko, Yoshiko; Uchino, Junichi; Takayama, K.

doi:10.21037/tlcr.2019.10.23

Cited by 65 publications

(62 citation statements)

References 18 publications

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“…Although there are studies correlating phylum Bacteroidetes with poor response from ICIs [12,17], we also observed several other studies were suggestive of a positive impact [6,13,18]. In fact, an earlier preclinical study demonstrated a cause and effect role of certain Bacteroidetes (e.g.…”

Section: Discussionsupporting

confidence: 48%

“…The vast majority are prospective studies. Among them, 10 studies [6,9,[12][13][14][15][16][17][18][19] had response/e cacy data and 3 studies [17,20,21] had AEs data using ICI therapy, and 1 study had both [17]. Of note, the documented AEs in that 3 studies [17,20,21] were virtually all irAEs.…”

Section: Common Features In Gut Microbiome Correlate With the Treatmementioning

confidence: 99%

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Relating Gut Microbiome and Its Modulating Factors to Immunotherapy in Solid Tumors: A Systematic Review

Huang

Liu

et al. 2020

Preprint

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Background: Gut microbiome is proved to affect the activity of immunotherapy in certain tumors. However, little is known if there is universal impact on both the treatment response and adverse effects (AEs) of immune checkpoint inhibitors (ICIs) across multiple solid tumors, and whether such impact can be modulated by common gut microbiome modifiers, such as antibiotics and diet.Methods: A systematic search in PubMed followed by stringent manual review were performed to identify clinical cohort studies that evaluated the relevance of gut microbiome to ICIs (response and/or AEs, 12 studies), or association of antibiotics with ICIs (17 studies), or impact of diet on gut microbiome (16 studies). Only original studies published in English before April 1st, 2020 were used. Qualified studies identified in the reference were also included.Results: At the phylum level, patients who had enriched abundance in Firmicutes and Verrucomicrobia almost universally had better response from ICIs, whereas those who were enriched in Proteobacteria universally presented with unfavorable outcome. Mixed correlations were observed for Bacteroidetes in relating to treatment response. Regarding the AEs, Firmicutes correlated to higher incidence whereas Bacteroidetes were clearly associated with less occurrence. Interestingly, across various solid tumors, majority of the studies suggested a negative association of antibiotic use with clinical response from ICIs, especially within 1-2 month prior to the initiation of ICIs. Finally, we observed a significant correlation of plant-based diet in relating to the enrichment of “ICI-favoring” gut microbiome (P = 0.0476).Conclusions: Gut microbiome may serve as a novel modifiable biomarker for both the treatment response and AEs of ICIs across various solid tumors. Further study is needed to understand the underlying mechanism, minimize the negative impact of antibiotics on ICIs, and gain insight regarding the role of diet so that this important lifestyle factor can be harnessed to improve the therapeutic outcomes of cancer immunotherapy partly through its impact on gut microbiome.

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Section: Discussionsupporting

confidence: 48%

Section: Common Features In Gut Microbiome Correlate With the Treatmementioning

confidence: 99%

Relating Gut Microbiome and Its Modulating Factors to Immunotherapy in Solid Tumors: A Systematic Review

Huang

Liu

et al. 2020

Preprint

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“…In addition, patients who were not responsive to ICI had more Staphylococcus present in their gut, a bacterium that is often elevated in cancer patients (9,36). In another study, patients with abundant Lactobacillus and Clostridium in their stool tended to have a longer benefit from ICI than those with a lower abundance (49). When assessing microbiota composition in the stool samples of patients with advanced NSCLC treated with nivolumab, subjects with high microbiome diversity had significantly longer progression-free survival compared to those with low diversity (50).…”

Section: Effects Of the Microbiome On Cancer Therapymentioning

confidence: 99%

The Role of the Microbiome in Cancer and Therapy Efficacy: Focus on Lung Cancer

et al. 2020

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The microbiome is extremely important for human health; more recently its role in the context of cancer became clear. Microbial effects range from enhancing cancer immunity and cancer therapy efficacy, to promoting cancer progression and inhibiting treatment efficacy. These broad implications led researchers to investigate these specific interactions, as well as how modification of the microbiome can improve cancer survival and treatment efficacy. While these interactions are better established for cancers such as gastric cancer, they are far less understood in others. As nonsmall cell lung cancer (NSCLC) makes up the majority of lung cancer cases, and is among the top causes of cancer deaths worldwide, understanding the mechanisms by which the microbiome may impact progression and treatment is crucial to improve patient survival and treatment response. A literature review was conducted to reveal the crosslink between human microbiome and lung cancer. This includes immune priming, induction of pro-or anti-tumor response, and the local effects of intra-tumoral microbiota. Overall, this is a complex multifactorial relationship, and there are broad implications as to how this knowledge can improve cancer treatment. Solutions include manipulation of the microbiome using probiotics, bacterial vaccines and antibiotics. Bacteria biomarkers may also be used as a diagnostic tool. The microbiome, defined as the collection of genomes from all the microorganisms found in a particular environment, is an emerging and widely studied factor in human health. Its implications in cancer are manifold (1). Specific microorganisms that are found within a specific environment (i.e., the microbiota) induce anti-tumor immunity through immune priming (1, 2). Dysbiosis, genotoxins, and inflammatory responses to microbiota are associated with cancer development (1). Additionally, cancer treatment efficacy can be enhanced or inhibited by intra-tumoral and gut microbiota (3-5). This knowledge leads to many questions regarding the interactions between the microbiome, cancer and cancer therapies. Most importantly, how can a better understanding of these interactions lead to improvement of current treatment efficacy? Compared to the gastrointestinal (GI) tract, the microbiota of the lung and other organs are far less understood (4, 6). Lung cancer is the first cause of death among oncologic patients and the second most common cancer worldwide (7). Investigating microbial-cancer relationships will aid in a better understanding of the role of microbes in mechanisms underlying tumorigenesis behind this as well as other cancers and hopefully improve treatment efficacy (4). These factors are poorly understood in lung cancer (3, 8, 9). Therefore, this review aims 4807 This article is freely accessible online.

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“…38,48 Furthermore, the relative abundance of members of the Ruminococcaceae family 48 correlated with the density of PD-1 + CD8 + T cells among (TILs). Again, another report analyzing the gut microbiota composition from 17 NSCLC patients revealed that Lactobacillus, Clostridium, and Syntrophococcus were overrepresented in R, while Bilophila or Sutterella 49 was dominant in NR. Of note, the presence of Bilophila drastically shortened the time to treatment failure.…”

Section: Gut Oncomicrobiota Signatures Associated With Response To Icismentioning

confidence: 99%

“…Of note, the presence of Bilophila drastically shortened the time to treatment failure. 49 A Chinese prospective study including 63 NSCLC cancer patients revealed Parabacteroides and Methanobacteriaceae as species and family members associated with PFS >6 months while stool enriched in Veillonella, Selenomonadales, and Negativicutes 50 predicted shorter PFS during PD-1 blockade. In sharp contrast with these findings, ileal enrichment with Veillonella, Selenomonadales, and Negativicutes was found to be associated with increased TIL and favorable prognosis during oxaliplatin-based chemotherapy in proximal colon cancer patients.…”

Section: Gut Oncomicrobiota Signatures Associated With Response To Icismentioning

confidence: 99%

Elucidating the gut microbiota composition and the bioactivity of immunostimulatory commensals for the optimization of immune checkpoint inhibitors

et al. 2020

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Accumulating evidence from preclinical studies and human trials demonstrated the crucial role of the gut microbiota in determining the effectiveness of anticancer therapeutics such as immunogenic chemotherapy or immune checkpoint blockade. In summary, it appears that a diverse intestinal microbiota supports therapeutic anticancer responses, while a dysbiotic microbiota composition that lacks immunostimulatory bacteria or contains overabundant immunosuppressive species causes treatment failure. In this review, we explore preclinical and translational studies highlighting how eubiotic and dysbiotic microbiota composition can affect progression-free survival in cancer patients.

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The role of the gut microbiome on the efficacy of immune checkpoint inhibitors in Japanese responder patients with advanced non-small cell lung cancer

Cited by 65 publications

References 18 publications

Relating Gut Microbiome and Its Modulating Factors to Immunotherapy in Solid Tumors: A Systematic Review

Relating Gut Microbiome and Its Modulating Factors to Immunotherapy in Solid Tumors: A Systematic Review

The Role of the Microbiome in Cancer and Therapy Efficacy: Focus on Lung Cancer

Elucidating the gut microbiota composition and the bioactivity of immunostimulatory commensals for the optimization of immune checkpoint inhibitors

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