Comparative analysis of the tumor microbiome, molecular profiles, and immune cell abundances by HPV status in mucosal head and neck cancers and their impact on survival

Head and Neck Squamous Cell Carcinoma (HNSCC) comprises a diverse group of tumors with variable treatment response and prognosis. The tumor microenvironment (TME), which includes microbiome and immune cells, can impact outcomes. Here, we sought to relate the presence of specific microbes, gene expre...

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Main Authors: Rituraj Upadhyay, Aastha Dhakal, Caroline Wheeler, Rebecca Hoyd, Malvenderjit Jagjit Singh, Vidhya Karivedu, Priyanka Bhateja, Marcelo Bonomi, Sasha Valentin, Mauricio E. Gamez, David J. Konieczkowski, Sujith Baliga, John C. Grecula, Dukagjin M. Blakaj, Emile Gogineni, Darrion L. Mitchell, Nicholas C. Denko, Daniel Spakowicz, Sachin R. Jhawar
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Cancer Biology & Therapy
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Online Access:https://www.tandfonline.com/doi/10.1080/15384047.2024.2350249
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author Rituraj Upadhyay
Aastha Dhakal
Caroline Wheeler
Rebecca Hoyd
Malvenderjit Jagjit Singh
Vidhya Karivedu
Priyanka Bhateja
Marcelo Bonomi
Sasha Valentin
Mauricio E. Gamez
David J. Konieczkowski
Sujith Baliga
John C. Grecula
Dukagjin M. Blakaj
Emile Gogineni
Darrion L. Mitchell
Nicholas C. Denko
Daniel Spakowicz
Sachin R. Jhawar
author_facet Rituraj Upadhyay
Aastha Dhakal
Caroline Wheeler
Rebecca Hoyd
Malvenderjit Jagjit Singh
Vidhya Karivedu
Priyanka Bhateja
Marcelo Bonomi
Sasha Valentin
Mauricio E. Gamez
David J. Konieczkowski
Sujith Baliga
John C. Grecula
Dukagjin M. Blakaj
Emile Gogineni
Darrion L. Mitchell
Nicholas C. Denko
Daniel Spakowicz
Sachin R. Jhawar
author_sort Rituraj Upadhyay
collection DOAJ
description Head and Neck Squamous Cell Carcinoma (HNSCC) comprises a diverse group of tumors with variable treatment response and prognosis. The tumor microenvironment (TME), which includes microbiome and immune cells, can impact outcomes. Here, we sought to relate the presence of specific microbes, gene expression, and tumor immune infiltration using tumor transcriptomics from The Cancer Genome Atlas (TCGA) and associate these with overall survival (OS). RNA sequencing (RNAseq) from HNSCC tumors in TCGA was processed through the exogenous sequences in tumors and immune cells (exotic) pipeline to identify and quantify low-abundance microbes. The detection of the Papillomaviridae family of viruses assessed HPV status. All statistical analyses were performed using R. A total of 499 RNAseq samples from TCGA were analyzed. HPV was detected in 111 samples (22%), most commonly Alphapapillomavirus 9 (90.1%). The presence of Alphapapillomavirus 9 was associated with improved OS [HR = 0.60 (95%CI: 0.40–0.89, p = .01)]. Among other microbes, Yersinia pseudotuberculosis was associated with the worst survival (HR = 3.88; p = .008), while Pseudomonas viridiflava had the best survival (HR = 0.05; p = .036). Microbial species found more abundant in HPV- tumors included several gram-negative anaerobes. HPV- tumors had a significantly higher abundance of M0 (p < .001) and M2 macrophages (p = .035), while HPV+ tumors had more T regulatory cells (p < .001) and CD8+ T-cells (p < .001). We identified microbes in HNSCC tumor samples significantly associated with survival. A greater abundance of certain anaerobic microbes was seen in HPV tumors and pro-tumorigenic macrophages. These findings suggest that TME can be used to predict patient outcomes and may help identify mechanisms of resistance to systemic therapies.
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spelling doaj-art-9cd2a6b3a01a4b8fbe8b5d225ed3cc932024-12-13T06:53:24ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762024-12-0125110.1080/15384047.2024.2350249Comparative analysis of the tumor microbiome, molecular profiles, and immune cell abundances by HPV status in mucosal head and neck cancers and their impact on survivalRituraj Upadhyay0Aastha Dhakal1Caroline Wheeler2Rebecca Hoyd3Malvenderjit Jagjit Singh4Vidhya Karivedu5Priyanka Bhateja6Marcelo Bonomi7Sasha Valentin8Mauricio E. Gamez9David J. Konieczkowski10Sujith Baliga11John C. Grecula12Dukagjin M. Blakaj13Emile Gogineni14Darrion L. Mitchell15Nicholas C. Denko16Daniel Spakowicz17Sachin R. Jhawar18Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USAThe Ohio State University College of Medicine, Columbus, OH, USADivision of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USADivision of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USADivision of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USADivision of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USADivision of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USADivision of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USADepartment of Dentistry, The Ohio State University Wexner Medical Center, Columbus, OH, USADepartment of Radiation Oncology, Mayo Clinic, Rochester, MN, USADepartment of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USADepartment of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USADepartment of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USADepartment of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USADepartment of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USADepartment of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USADepartment of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USADivision of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USADepartment of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USAHead and Neck Squamous Cell Carcinoma (HNSCC) comprises a diverse group of tumors with variable treatment response and prognosis. The tumor microenvironment (TME), which includes microbiome and immune cells, can impact outcomes. Here, we sought to relate the presence of specific microbes, gene expression, and tumor immune infiltration using tumor transcriptomics from The Cancer Genome Atlas (TCGA) and associate these with overall survival (OS). RNA sequencing (RNAseq) from HNSCC tumors in TCGA was processed through the exogenous sequences in tumors and immune cells (exotic) pipeline to identify and quantify low-abundance microbes. The detection of the Papillomaviridae family of viruses assessed HPV status. All statistical analyses were performed using R. A total of 499 RNAseq samples from TCGA were analyzed. HPV was detected in 111 samples (22%), most commonly Alphapapillomavirus 9 (90.1%). The presence of Alphapapillomavirus 9 was associated with improved OS [HR = 0.60 (95%CI: 0.40–0.89, p = .01)]. Among other microbes, Yersinia pseudotuberculosis was associated with the worst survival (HR = 3.88; p = .008), while Pseudomonas viridiflava had the best survival (HR = 0.05; p = .036). Microbial species found more abundant in HPV- tumors included several gram-negative anaerobes. HPV- tumors had a significantly higher abundance of M0 (p < .001) and M2 macrophages (p = .035), while HPV+ tumors had more T regulatory cells (p < .001) and CD8+ T-cells (p < .001). We identified microbes in HNSCC tumor samples significantly associated with survival. A greater abundance of certain anaerobic microbes was seen in HPV tumors and pro-tumorigenic macrophages. These findings suggest that TME can be used to predict patient outcomes and may help identify mechanisms of resistance to systemic therapies.https://www.tandfonline.com/doi/10.1080/15384047.2024.2350249Tumor microbiomemolecular profilesimmune cell abundancesHPVHNSCCmicrobiome
spellingShingle Rituraj Upadhyay
Aastha Dhakal
Caroline Wheeler
Rebecca Hoyd
Malvenderjit Jagjit Singh
Vidhya Karivedu
Priyanka Bhateja
Marcelo Bonomi
Sasha Valentin
Mauricio E. Gamez
David J. Konieczkowski
Sujith Baliga
John C. Grecula
Dukagjin M. Blakaj
Emile Gogineni
Darrion L. Mitchell
Nicholas C. Denko
Daniel Spakowicz
Sachin R. Jhawar
Comparative analysis of the tumor microbiome, molecular profiles, and immune cell abundances by HPV status in mucosal head and neck cancers and their impact on survival
Cancer Biology & Therapy
Tumor microbiome
molecular profiles
immune cell abundances
HPV
HNSCC
microbiome
title Comparative analysis of the tumor microbiome, molecular profiles, and immune cell abundances by HPV status in mucosal head and neck cancers and their impact on survival
title_full Comparative analysis of the tumor microbiome, molecular profiles, and immune cell abundances by HPV status in mucosal head and neck cancers and their impact on survival
title_fullStr Comparative analysis of the tumor microbiome, molecular profiles, and immune cell abundances by HPV status in mucosal head and neck cancers and their impact on survival
title_full_unstemmed Comparative analysis of the tumor microbiome, molecular profiles, and immune cell abundances by HPV status in mucosal head and neck cancers and their impact on survival
title_short Comparative analysis of the tumor microbiome, molecular profiles, and immune cell abundances by HPV status in mucosal head and neck cancers and their impact on survival
title_sort comparative analysis of the tumor microbiome molecular profiles and immune cell abundances by hpv status in mucosal head and neck cancers and their impact on survival
topic Tumor microbiome
molecular profiles
immune cell abundances
HPV
HNSCC
microbiome
url https://www.tandfonline.com/doi/10.1080/15384047.2024.2350249
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