Abstract 5907: The tumor microbiome associates with features of the tumor microenvironment, treatment outcomes, and histologies: A national collaboration of the exORIEN Consortium
Authors: Hoyd Rebecca , Wheeler Caroline E. , Coleman Samuel , Denko Louis , Chan Carlos , Zakharia Yousef , Dodd Rebecca , Ulrich Cornelia M. , Hardikar Sheetal , Ose Jennifer , Churchman Michelle , Tarhini Ahmad , Robinson Lary A. , Singer Eric , Ikeguchi Alexandra P. , McCarter Martin , Anderson Kyra , Carpten John , Tinoco Gabriel , Hussain Marium , Denko Nicolas , Liu YunZhou , Jin Ning , Kim Youngchul , Masson Asgeir , Fei Naomi , Benej Martin , Kreamer McKenzie , Grencewicz Dennis Dennis , Hussein Ahmed , Tan Aik Choon , Spakowicz Daniel 
Published: June 2023

Abstract
A tumor microbiome has recently been established as present in many cancer types. Further study is needed to define the scope of its role in cancer tumorigenesis, progression, and treatment outcomes. The Oncology Research Information Exchange Network (ORIEN) established a collaboration among eight member institutions to study the tumor microbiome and clinical features across several cancers. We evaluated RNAseq data from n = 2,892 tumors, including colorectal adenocarcinomas, lung adeno- and squamous cell carcinomas, pancreatic adenocarcinomas, sarcomas, melanomas, and thyroid carcinomas, using the tool {exotic}. Matched cancers from the Cancer Genome Atlas were processed by the same method (n = 2,720 samples). Clinical data, including treatment information, lab values, detailed histology, and long-term follow-up, were collected and harmonized across sites. Microbe abundances (bacteria, fungi, and viruses) were associated with clinical features and human gene expression, which was deconvolved into immune cell composition using {CIBERSORT} and {TIMEx}, and aggregated into expression signatures using {tmesig} and {IOSig}. Microbes were found in all tumors and associated with treatment outcomes for all modalities tested, including radiation in colorectal cancer, chemotherapy in pancreatic cancer, and immunotherapy in melanoma. In the case of radiation treatment in colorectal cancer, the microbes also affected outcomes in preclinical model systems and were modified by altering hypoxia levels with the drug atovaquone. Virus prevalence associated with histological subtypes in lung cancer. Similar microbes in ORIEN and TCGA tumors associated with overall survival in subtypes of sarcoma (dedifferentiated liposarcoma, leiomyosarcoma, and others). Finally, microbes associated with expression-based indicators of the tumor microenvironment across cancer types. These results suggest that the tumor microbiome may have broad clinical utility as a biomarker of treatment outcomes and as a target for rational manipulation.
Citation Format: Rebecca Hoyd, Caroline E. Wheeler, Samuel Coleman, Louis Denko, Carlos Chan, Yousef Zakharia, Rebecca Dodd, Cornelia M. Ulrich, Sheetal Hardikar, Jennifer Ose, Michelle Churchman, Ahmad Tarhini, Lary A. Robinson, Eric Singer, Alexandra P. Ikeguchi, Martin McCarter, Kyra Anderson, John Carpten, Gabriel Tinoco, Marium Hussain, Nicolas Denko, YunZhou Liu, Ning Jin, Youngchul Kim, Asgeir Masson, Naomi Fei, Martin Benej, McKenzie Kreamer, Dennis Dennis Grencewicz, Ahmed Hussein, Aik Choon Tan, Daniel Spakowicz. The tumor microbiome associates with features of the tumor microenvironment, treatment outcomes, and histologies: A national collaboration of the exORIEN Consortium. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5907.