The Tumor Microbiome as a Predictor of Outcomes in Patients with Metastatic Melanoma Treated with Immune Checkpoint Inhibitors.

Autor:	Dravillas CE; Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Coleman SS 4th; 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., Hoyd R; Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Caryotakis G; 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., Denko L; Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.; Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Chan CHF; Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa., Churchman ML; Aster Insights, Hudson, Florida., Denko N; Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Dodd RD; Department of Internal Medicine, University of Iowa, Iowa City, Iowa., Eljilany I; Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida., Hardikar S; Department of Population Health Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah., Husain M; Division of Medical 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., Jin N; Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Ma Q; Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio., McCarter MD; Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado., Osman AEG; Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah, Salt Lake City, Utah., Robinson LA; Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida., Singer EA; Division of Urologic Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Tinoco G; Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Ulrich CM; Department of Population Health Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah., Zakharia Y; Division of Oncology, Hematology and Blood and Marrow Transplantation, University of Iowa, Holden Comprehensive Cancer Center, Iowa City, Iowa., Spakowicz D; Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.; Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., 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., 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.
Jazyk:	angličtina
Zdroj:	Cancer research communications [Cancer Res Commun] 2024 Aug 01; Vol. 4 (8), pp. 1978-1990.
DOI:	10.1158/2767-9764.CRC-23-0170
Abstrakt:	Emerging evidence supports the important role of the tumor microbiome in oncogenesis, cancer immune phenotype, cancer progression, and treatment outcomes in many malignancies. In this study, we investigated the metastatic melanoma tumor microbiome and its potential roles in association with clinical outcomes, such as survival, in patients with metastatic disease treated with immune checkpoint inhibitors (ICI). Baseline tumor samples were collected from 71 patients with metastatic melanoma before treatment with ICIs. Bulk RNA sequencing (RNA-seq) was conducted on the formalin-fixed, paraffin-embedded and fresh frozen tumor samples. Durable clinical benefit (primary clinical endpoint) following ICIs was defined as overall survival >24 months and no change to the primary drug regimen (responders). We processed RNA-seq reads to carefully identify exogenous sequences using the {exotic} tool. The age of the 71 patients with metastatic melanoma ranged from 24 to 83 years, 59% were male, and 55% survived >24 months following the initiation of ICI treatment. Exogenous taxa were identified in the tumor RNA-seq, including bacteria, fungi, and viruses. We found differences in gene expression and microbe abundances in immunotherapy-responsive versus nonresponsive tumors. Responders showed significant enrichment of bacteriophages in the phylum Uroviricota, and nonresponders showed enrichment of several bacteria, including Campylobacter jejuni. These microbes correlated with immune-related gene expression signatures. Finally, we found that models for predicting prolonged survival with immunotherapy using both microbe abundances and gene expression outperformed models using either dataset alone. Our findings warrant further investigation and potentially support therapeutic strategies to modify the tumor microbiome in order to improve treatment outcomes with ICIs. Significance: We analyzed the tumor microbiome and interactions with genes and pathways in metastatic melanoma treated with immunotherapy and identified several microbes associated with immunotherapy response and immune-related gene expression signatures. Machine learning models that combined microbe abundances and gene expression outperformed models using either dataset alone in predicting immunotherapy responses. (©2024 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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