Modulatory effects of gut microbiome in cancer immunotherapy: A novel paradigm for blockade of immune checkpoint inhibitors

Rezasoltani, Sama; Yadegar, Abbas; Aghdaei, Hamid Asadzadeh; Zali, Mohammad Reza

doi:10.1002/cam4.3694

Cited by 39 publications

(34 citation statements)

References 134 publications

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“…Our reporting of an association between the gut microbiome and immunotherapy outcomes and irAEs in advanced cancer patients is consistent with the results of previous studies [ 29 , 30 , 31 ]. Several studies examining the relationships between the diversity and composition of the gut microbiome and AEs and clinical response during chemotherapy [ 29 ], radiotherapy [ 32 ] and immunotherapy [ 33 ], identified that dysbiosis of the microbiome was related to AEs and clinical response to cancer therapies. These studies suggested that the gut microbiome prior to cancer treatment can be used as a predictor of clinical response and AEs and recommended that assessment of the microbiome in cancer therapy could improve patient care [ 15 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…The current review is significant in that it included only clinical studies in order to provide updated meaningful evidence for clinicians, cancer patients and carers, whereas previous reviews, examining both animal models and clinical studies in order to elucidate the role of gut microbiota in ICIs, resulted in gaps in their application to real-world clinical practice [ 33 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

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The Gut Microbiome and Cancer Immunotherapy: Can We Use the Gut Microbiome as a Predictive Biomarker for Clinical Response in Cancer Immunotherapy?

Boyle

Pavlakis

et al. 2021

Cancers

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Background: Emerging evidence suggests that gut microbiota influences the clinical response to immunotherapy. This review of clinical studies examines the relationship between gut microbiota and immunotherapy outcomes. Method: A literature search was conducted in electronic databases Medline, PubMed and ScienceDirect, with searches for “cancer” and “immunotherapy/immune checkpoint inhibitor” and “microbiome/microbiota” and/or “fecal microbiome transplant FMT”. The relevant literature was selected for this article. Results: Ten studies examined patients diagnosed with advanced metastatic melanoma (n = 6), hepatocellular carcinoma (HCC) (n = 2), non-small cell lung carcinoma (NSCLC) (n = 1) and one study examined combination both NSCLC and renal cell carcinoma (RCC) (n = 1). These studies consistently reported that the gut microbiome profile prior to administering immune checkpoint inhibitors (ICIs) was related to clinical response as measured by progression-free survival (PFS) and overall survival (OS). Two studies reported that a low abundance of Bacteroidetes was associated with colitis. Two studies showed that patients with anti-PD-1 refractory metastatic melanoma experienced improved response rates and no added toxicity when receiving fecal microbiota transplant (FMT) from patients with anti-PD-1 responsive disease. Conclusions: Overall, significant differences in the diversity and composition of the gut microbiome were identified in ICIs responders and non-responders. Our findings provide new insights into the value of assessing the gut microbiome in immunotherapy. Further robust randomized controlled trials (RCTs) examining the modulatory effects of the gut microbiome and FMT on ICIs in patients not responding to immunotherapy are warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Gut Microbiome and Cancer Immunotherapy: Can We Use the Gut Microbiome as a Predictive Biomarker for Clinical Response in Cancer Immunotherapy?

Boyle

Pavlakis

et al. 2021

Cancers

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“…The immune response in cancer therapy was improved by the inhibition of regulatory T cells (Tregs) through Bifidobacterium adolescentis , Enterococcus faecium, Collinsella aerofaciens and Parabacteroides merdae [ 74 ]. The gut microbiota has been shown to increase the efficacy of blockade therapy of programmed cell death 1 (PD-1) protein and its ligand, programmed cell death ligand 1 (PD-L1) [ 80 ]. On the contrary, the anticancer immune response increased and the tumor burden was reduced by depletion of the gut microbiota through oral gavage antibiotics treatment in a mouse model of PC [ 81 ].…”

Section: The Microbiota and Drug Response In Pcmentioning

confidence: 99%

“…However, their mechanisms in enhancing or attenuating the efficacy of immunotherapies need to be identified. Through fecal microbiota transplant (FMT) or supplementation with certain prebiotics, probiotics, or antibiotics, the gut microbial composition could be manipulated to enhance host anticancer immunity and combat drug resistance [ 80 ]. Moreover, the gut microbiota could be used as a biomarker for drug efficacy, treatment response and drug side effects [ 74 ].…”

Section: The Microbiota and Drug Response In Pcmentioning

confidence: 99%

Microbiota Alterations and Their Association with Oncogenomic Changes in Pancreatic Cancer Patients

Sammallahti

Kokkola

Rezasoltani

et al. 2021

IJMS

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Pancreatic cancer (PC) is an aggressive disease with a high mortality and poor prognosis. The human microbiome is a key factor in many malignancies, having the ability to alter host metabolism and immune responses and participate in tumorigenesis. Gut microbes have an influence on physiological functions of the healthy pancreas and are themselves controlled by pancreatic secretions. An altered oral microbiota may colonize the pancreas and cause local inflammation by the action of its metabolites, which may lead to carcinogenesis. The mechanisms behind dysbiosis and PC development are not completely clear. Herein, we review the complex interactions between PC tumorigenesis and the microbiota, and especially the question, whether and how an altered microbiota induces oncogenomic changes, or vice versa, whether cancer mutations have an impact on microbiota composition. In addition, the role of the microbiota in drug efficacy in PC chemo- and immunotherapies is discussed. Possible future scenarios are the intentional manipulation of the gut microbiota in combination with therapy or the utilization of microbial profiles for the noninvasive screening and monitoring of PC.

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“…Immunotherapy with checkpoint inhibitors, including CTLA-4 and PD-1 inhibitors, are recent additions to the armament of medical oncologists, and have shown impressive responses in people with tumors non-responsive to traditional cytotoxic chemotherapy 52 . These agents favor antitumor T-cell proliferation and stimulation of the immune system partially via depletion of Regulatory T (TReg) cells, which can inhibit normal immune function.…”

Section: The Microbiome and Cancer Treatmentmentioning

confidence: 99%

Prospective evaluation of the fecal microbiome in dogs with large-cell lymphoma receiving chop chemotherapy

Couto¹

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The fecal microbiome composition has been associated with reduced efficacy of cancer therapy and adverse side effects in humans, and chemotherapy has been shown to alter the gut microbiome. The relationship between microbiota and chemotherapy efficacy and tolerability has not been investigated in dogs. We aimed to evaluate changes in fecal microbial diversity during a cycle of CHOP chemotherapy in dogs with lymphoma and whether these changes correlated with adverse events or treatment response. Eighteen dogs with lymphoma were prospectively enrolled, and stool samples were acquired weekly for 6 weeks during CHOP. Fecal samples was analyzed via 16S rRNA amplicon sequencing as previously described. Treatment-associated differences in richness, alpha and beta diversity were determined through comparison to data from healthy controls (n = 26) using factorial ANOVA and PERMANOVA. Dogs with lymphoma had decreased fecal microbial diversity when compared with healthy controls at baseline and throughout treatment (p= 0.0002, 0.0003, 0.0001). Alpha and beta diversity did not significantly change in dogs throughout a cycle of CHOP chemotherapy (p = 0.520 and 0.995). Samples pre-treated with antibiotics were significantly less diverse (alpha and beta diversity) than untreated samples (p = 0.002, 0.0001 respectively). Dogs with lymphoma and fecal samples under the presence of antibiotics had higher levels of Escherchia species in their feces compared to normal dogs. The fecal microbiome of healthy dogs and dogs with lymphoma receiving CHOP is relatively stable over time, but dogs with lymphoma have reduced microbial diversity compared to healthy dogs before and during treatment. An increase in Proteobacteria abundance during treatment may be related to chemotherapy and/or antibiotic use.

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Modulatory effects of gut microbiome in cancer immunotherapy: A novel paradigm for blockade of immune checkpoint inhibitors

Cited by 39 publications

References 134 publications

The Gut Microbiome and Cancer Immunotherapy: Can We Use the Gut Microbiome as a Predictive Biomarker for Clinical Response in Cancer Immunotherapy?

The Gut Microbiome and Cancer Immunotherapy: Can We Use the Gut Microbiome as a Predictive Biomarker for Clinical Response in Cancer Immunotherapy?

Microbiota Alterations and Their Association with Oncogenomic Changes in Pancreatic Cancer Patients

Prospective evaluation of the fecal microbiome in dogs with large-cell lymphoma receiving chop chemotherapy

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