The Tumor Microbiome Reacts to Hypoxia and Can Influence Response to Radiation Treatment in Colorectal Cancer.

Autor:	Benej M; Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Hoyd R; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Kreamer M; Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Wheeler CE; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Grencewicz DJ; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Choueiry F; Department of Health Sciences, The Ohio State University, Columbus, Ohio., Chan CHF; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa., Zakharia Y; Division of Oncology, Hematology and Blood & Marrow Transplantation, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa., Ma Q; Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio.; Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Dodd RD; Department of Internal Medicine, University of Iowa, Iowa City, Iowa., Ulrich CM; Department of Population Health Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah., Hardikar S; Department of Population Health Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah., Churchman ML; Aster Insights, Hudson, Florida., Tarhini AA; Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.; Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida., Robinson LA; Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida., Singer EA; Department of Urologic Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Ikeguchi AP; Department of Hematology/Oncology, Stephenson Cancer Center of University of Oklahoma, Oklahoma City, Oklahoma., McCarter MD; Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado., Tinoco G; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Husain M; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Jin N; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Tan AC; Department of Oncological Science, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.; Department of Biomedical Informatics, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah., Osman AEG; Department of Internal Medicine, University of Utah, Salt Lake City, Utah., Eljilany I; Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.; Clinical Science Lab, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida., Riedlinger G; Department of Precision Medicine, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey., Schneider BP; Indiana University Simon Comprehensive Cancer Center, Indianapolis, Indiana., Benejova K; Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Kery M; Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Papandreou I; Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Zhu J; Department of Health Sciences, The Ohio State University, Columbus, Ohio., Denko N; Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Spakowicz D; Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.; Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.
Jazyk:	angličtina
Zdroj:	Cancer research communications [Cancer Res Commun] 2024 Jul 01; Vol. 4 (7), pp. 1690-1701.
DOI:	10.1158/2767-9764.CRC-23-0367
Abstrakt:	Tumor hypoxia has been shown to predict poor patient outcomes in several cancer types, partially because it reduces radiation's ability to kill cells. We hypothesized that some of the clinical effects of hypoxia could also be due to its impact on the tumor microbiome. Therefore, we examined the RNA sequencing data from the Oncology Research Information Exchange Network database of patients with colorectal cancer treated with radiotherapy. We identified microbial RNAs for each tumor and related them to the hypoxic gene expression scores calculated from host mRNA. Our analysis showed that the hypoxia expression score predicted poor patient outcomes and identified tumors enriched with certain microbes such as Fusobacterium nucleatum. The presence of other microbes, such as Fusobacterium canifelinum, predicted poor patient outcomes, suggesting a potential interaction between hypoxia, the microbiome, and radiation response. To experimentally investigate this concept, we implanted CT26 colorectal cancer cells into immune-competent BALB/c and immune-deficient athymic nude mice. After growth, in which tumors passively acquired microbes from the gastrointestinal tract, we harvested tumors, extracted nucleic acids, and sequenced host and microbial RNAs. We stratified tumors based on their hypoxia score and performed a metatranscriptomic analysis of microbial gene expression. In addition to hypoxia-tropic and -phobic microbial populations, analysis of microbial gene expression at the strain level showed expression differences based on the hypoxia score. Thus, hypoxia gene expression scores seem to associate with different microbial populations and elicit an adaptive transcriptional response in intratumoral microbes, potentially influencing clinical outcomes. Significance: Tumor hypoxia reduces radiotherapy efficacy. In this study, we explored whether some of the clinical effects of hypoxia could be due to interaction with the tumor microbiome. Hypoxic gene expression scores associated with certain microbes and elicited an adaptive transcriptional response in others that could contribute to poor clinical outcomes. (©2024 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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