Abstract 2838: The gut microbiome (GM) and immunotherapy response are influenced by host lifestyle factors

Spencer, Christine N.; Gopalakrishnan, Vancheswaran; McQuade, Jennifer L.; Andrews, Miles C.; Helmink, Beth A.; Khan, Muhammad Ali; Sirmans, Elizabeth; Haydu, Lauren E.; Cogdill, Alexandria P.; Burton, Elizabeth M.; Amaria, Rodabe N.; Patel, Sapna; Glitza, Isabella C.; Davies, Michael A.; Posada, Eliza; Hwu, Wen‐Jen; Diab, Adi; Nelson, Kelly A.; Tawbi, Hussein Abdul-Hassan; Wong, Michael L.; Jenq, Robert R.; Cohen, Lorenzo; Daniel, Carrie R.; Wargo, Jennifer A.

doi:10.1158/1538-7445.sabcs18-2838

Cited by 35 publications

(49 citation statements)

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“…Despite the lack of direct evidence, we did observe that plant-based diet enriched "ICI-favoring" gut microbiome, represented as increased Firmicutes or Verrucomicrobia or α diversity, or reduced abundance of Proteobacteria. Such nding is consistent with a recent study on melanoma patients demonstrating that the response to immunotherapy can be in uenced by dietary manipulation [37] -patients who consumed a high-ber diet (plant-based) were about ve times as likely to respond to anti-PD-1 treatment compared to patients who consumed a low-ber diet [37]. Further studies are warranted to clarify the potential value of diet/nutrition in both the treatment response and irAEs of cancer immunotherapy.…”

Section: Discussionsupporting

confidence: 92%

“…Using search keywords "diet" or "nutrition", "microbiome", "cancer" and "immunotherapy", and their combinations, we were not able to extract su cient number of clinical studies that directly link diet to cancer immunotherapy, including those published in abstract format [37], which is suggestive of an unmet need in this area. Since gut microbiome impacts cancer immunotherapy, we then investigated whether diet will have effect on gut microbiome that could potentially affect cancer immunotherapy.…”

Section: Diet Could Potentially Affect the E Cacy Of Cancer Immunothementioning

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: 92%

Section: Diet Could Potentially Affect the E Cacy Of Cancer Immunothementioning

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 a single-center study of patients treated for melanoma, those with higher fiber intake had better ICI responses, but those who used probiotics had lower alpha diversity, and were less likely to respond to ICI in a subset analysis. 128 While broad over-the-counter probiotic administration in patients receiving ICI is to be avoided, trials of specific bacterial manipulation are ongoing, including using tailored probiotic administration (NCT03829111) and dietary modifications. Fecal transplant as a means to transfer the diverse bacterial ecosystem from responders to non-responders is also an area of great interest.…”

Section: Indirect Modulation Of Tumor Immunogenicity Markers Of An Immentioning

confidence: 99%

The future of cancer immunotherapy: microenvironment-targeting combinations

2020

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Immunotherapy holds the potential to induce durable responses, but only a minority of patients currently respond. The etiologies of primary and secondary resistance to immunotherapy are multifaceted, deriving not only from tumor intrinsic factors, but also from the complex interplay between cancer and its microenvironment. In addressing frontiers in clinical immunotherapy, we describe two categories of approaches to the design of novel drugs and combination therapies: the first involves direct modification of the tumor, while the second indirectly enhances immunogenicity through alteration of the microenvironment. By systematically addressing the factors that mediate resistance, we are able to identify mechanistically-driven novel approaches to improve immunotherapy outcomes.

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“…Conversely, non-responders were reported to have a diet rich in processed sugars and processed meats. It is argued that a high-fiber diet promotes a diverse microbiota and a gut flora rich in Ruminococcaceae species [ 28 ]. This favorable flora likely promotes higher levels of circulating CD8+ T cells and APCs, which is critical to the efficacy of CPIs.…”

Section: Immunotherapymentioning

confidence: 99%

Understanding the Mechanisms of Diet and Outcomes in Colon, Prostate, and Breast Cancer; Malignant Gliomas; and Cancer Patients on Immunotherapy

2020

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Cancer patients often ask which foods would be best to consume to improve outcomes. This is a difficult question to answer as there are no case-controlled, prospective studies that control for confounding factors. Therefore, a literature review utilizing PubMed was conducted with the goal to find evidence-based support for certain diets in specific cancer patients—specifically, we reviewed data for colon cancer, prostate cancer, breast cancer, malignant gliomas, and cancer patients on immunotherapy. Improved outcomes in colon cancer and patients on immunotherapy were found with high-fiber diets. Improved outcomes in malignant gliomas were found with ketogenic diets. Improved outcomes in prostate cancer and breast cancer were found with plant-based diets. However, the data are not conclusive for breast cancer. Additionally, the increased intake of omega-3 fatty acids were also associated with better outcomes for prostate cancer. While current research, especially in humans, is minimal, the studies discussed in this review provide the groundwork for future research to further investigate the role of dietary intervention in improving cancer outcomes.

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Abstract 2838: The gut microbiome (GM) and immunotherapy response are influenced by host lifestyle factors

Cited by 35 publications

References 0 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 future of cancer immunotherapy: microenvironment-targeting combinations

Understanding the Mechanisms of Diet and Outcomes in Colon, Prostate, and Breast Cancer; Malignant Gliomas; and Cancer Patients on Immunotherapy

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