The Microbiome as a Component of the Tumor Microenvironment

Kovàcs, Tündé; Mikó, Edit; Ujlaki, Gyula; Sári, Zsanett; Bai, Péter

doi:10.1007/978-3-030-35727-6_10

Cited by 73 publications

(64 citation statements)

References 74 publications

(90 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our results identify that in the setting of an altered microbiome, response to platinum chemotherapy is reduced and populations of chemo-resistance cancer stem cells are increased through tumorsphere initiation frequency and transcriptional reprogramming to an increased cancer stem cell-like state. The relationship between enhanced populations of cancer stem cells and platinum resistance in EOC is well-documented in the literature (28,45,48,(51)(52)(53)(54). Specifically, we identified SOX2, WNT7a, HOXb5, HOXb6, DLX5, MSX1, EFNA4, SALL1, and PAX2 as being significantly upregulated in ID8 tumors of the ABX group over the control H 2 O group.…”

Section: Discussionmentioning

confidence: 64%

“…The majority of EOC patients present with advanced disease (stage III or stage IV) that may include ascites (25,26). Although the underlying mechanisms of ascites development are largely unknown, previous studies have reported that immune cells such as Th17 T cells, NK cells and macrophages found in peritoneal ascites may play a key role in tumor cell invasiveness and growth (27)(28)(29)(30). To this end, we analyzed the immune cell populations within the peritoneal ascites fluid through flow cytometry.…”

Section: Limited Impact On Immune Populations In Ascites Of Eoc By Brmentioning

confidence: 99%

See 1 more Smart Citation

Disruption of the gut microbiota attenuates epithelial ovarian cancer sensitivity to cisplatin therapy

Chambers

Esakov

Braley

et al. 2020

Preprint

View full text Add to dashboard Cite

Epithelial Ovarian Cancer (EOC) is the second most common gynecologic malignancy in the United States, but the leading cause of gynecologic cancer death. Despite many achieving remission with first-line therapy (cytoreductive surgery and platinum-taxane chemotherapy), up to 80% of patients will recur and require additional treatment. Antibiotic therapy is frequently used during cancer treatments for both prophylaxis and treatment of infections. We assessed whether antibiotics would impact growth of EOC and sensitivity to cisplatin in murine models. Murine ID8 or ID8-VEGF EOC that were injected intraperitoneally exhibited accelerated growth and augmented cisplatin resistance following treatment with antibiotics (ABX) in both C57 BL/6J and NSG mice, indicating this effect was independent of an intact immune system. While antibiotics are critical for the care of the patient, they profoundly impacted the microbiome. RNAseq analysis of ID8 tumors from the NSG ABX groups showed enrichment of multiple cell proliferation and stem cell pathways, and increased expression of common stem cell genes such as SOX2, WNT and PAX2. The cancer stem cell population was increased with antibiotic treatment and further augmented by cisplatin treatment. Collectively, these studies indicate an intact microbiome provides a tumor suppressive microenvironment and enhances sensitivity to cisplatin.

show abstract

Section: Discussionmentioning

confidence: 64%

Section: Limited Impact On Immune Populations In Ascites Of Eoc By Brmentioning

confidence: 99%

Disruption of the gut microbiota attenuates epithelial ovarian cancer sensitivity to cisplatin therapy

Chambers

Esakov

Braley

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Our results identify that in the setting of an altered microbiome, response to platinum chemotherapy is reduced and populations of chemo-resistance cancer stem cells are increased through tumorsphere initiation frequency and transcriptional reprogramming to an increased cancer stem cell-like state. The relationship between enhanced populations of cancer stem cells and platinum resistance in EOC is well-documented in the literature (28,45,48,(51)(52)(53)(54). Speci cally, we identi ed SOX2, WNT7a, HOXb5, HOXb6, DLX5, MSX1, EFNA4, SALL1, and PAX2 as being signi cantly upregulated in ID8 tumors of the ABX group over the control H 2 O group.…”

Section: Discussionmentioning

confidence: 70%

“…Although the underlying mechanisms of ascites development are largely unknown, previous studies have reported that immune cells such as Th17 T cells, NK cells and macrophages found in peritoneal ascites may play a key role in tumor cell invasiveness and growth (27)(28)(29)(30). To this end, we analyzed the immune cell populations within the peritoneal ascites uid through ow cytometry.…”

Section: Resultsmentioning

confidence: 99%

Disruption of the Gut Microbiota Attenuates Epithelial Ovarian Cancer Sensitivity to Cisplatin Therapy

Chambers¹,

Esakov

Braley

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Epithelial Ovarian Cancer (EOC) is the second most common gynecologic malignancy in the United States, but the leading cause of gynecologic cancer death. Despite many achieving remission with first-line therapy, up to 80% of patients will recur and require additional treatment. Antibiotic therapy is frequently used during cancer treatments for both prophylaxis and treatment of infections, although this profoundly impacts the gut microbiome. Multiple studies suggest that an unperturbed gut microbiome may provide a protective microenvironment, and disruption may be permissive to tumor growth and chemotherapy resistance, including platinum agents. Experimental Design: We assessed whether antibiotic therapy would impact growth of EOC and sensitivity to cisplatin in murine models. Immune competent or compromised mice were given either metronidazole, ampicillin, vancomycin, and neomycin (ABX) containing or control water for two weeks before being intraperitoneally injected with murine ID8 or ID8-VEGF EOC cells. Tumors were monitored and cisplatin therapy was administered weekly until endpoint. Stool was collected throughout the study to asses for microbial population effects over time.Results: Both immune competent and immune compromised ID8 and ID8 VEGF tumor-bearing mice demonstrated a decreased response to cisplatin therapy in ABX treated groups with an increase in overall tumor burden. RNAseq analysis showed enrichment of multiple cell proliferation and stem cell pathways, and stem cell genes SOX2, WNT and PAX2. The self-renewal of ABX treated tumor cells was also increased.Conclusion: Collectively, these studies indicate an intact microbiome provides a tumor suppressive microenvironment and enhances sensitivity to cisplatin.

show abstract

“…Bacterial metabolites modulate the redox balance of cancer cells [24,34], as well as cancer cell metabolism [22,23]. These processes culminate in cytostasis, a reprogramming of the epithelial-mesenchymal transition leading to decreased cancer stem cells [22][23][24][25]29,34,35,45]. These basic events are the pillars for the inhibition of cancer cell growth, movement, and metastasis formation [46][47][48].…”

Section: Pancreatic Adenocarcinoma An Unmet Medical Needmentioning

confidence: 99%

Oncobiosis and Microbial Metabolite Signaling in Pancreatic Adenocarcinoma

Kiss

Mikó

Sebő³

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Cite

Pancreatic adenocarcinoma is one of the most lethal cancers in both men and women, with a median five-year survival of around 5%. Therefore, pancreatic adenocarcinoma represents an unmet medical need. Neoplastic diseases, such as pancreatic adenocarcinoma, often are associated with microbiome dysbiosis, termed oncobiosis. In pancreatic adenocarcinoma, the oral, duodenal, ductal, and fecal microbiome become dysbiotic. Furthermore, the pancreas frequently becomes colonized (by Helicobacter pylori and Malassezia, among others). The oncobiomes from long- and short-term survivors of pancreatic adenocarcinoma are different and transplantation of the microbiome from long-term survivors into animal models of pancreatic adenocarcinoma prolongs survival. The oncobiome in pancreatic adenocarcinoma modulates the inflammatory processes that drive carcinogenesis. In this review, we point out that bacterial metabolites (short chain fatty acids, secondary bile acids, polyamines, indole-derivatives, etc.) also have a role in the microbiome-driven pathogenesis of pancreatic adenocarcinoma. Finally, we show that bacterial metabolism and the bacterial metabolome is largely dysregulated in pancreatic adenocarcinoma. The pathogenic role of additional metabolites and metabolic pathways will be identified in the near future, widening the scope of this therapeutically and diagnostically exploitable pathogenic pathway in pancreatic adenocarcinoma.

show abstract

The Microbiome as a Component of the Tumor Microenvironment

Abstract: Microbes, which live in the human body, affect a large set of pathophysiological processes. Changes in the composition and proportion of the microbiome are associated with metabolic diseases (

Cited by 73 publications

References 74 publications

Disruption of the gut microbiota attenuates epithelial ovarian cancer sensitivity to cisplatin therapy

Disruption of the gut microbiota attenuates epithelial ovarian cancer sensitivity to cisplatin therapy

Disruption of the Gut Microbiota Attenuates Epithelial Ovarian Cancer Sensitivity to Cisplatin Therapy

Oncobiosis and Microbial Metabolite Signaling in Pancreatic Adenocarcinoma

Contact Info

Product

Resources

About