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The Gut and Cervical Microbiome Promote Immune Activation and Response to Chemoradiation in Cervical Cancer

49 Pages Posted: 20 Jun 2018 Sneak Peek Status: Review Complete

See all articles by Lauren E. Colbert

Lauren E. Colbert

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

Megan Mikkelson

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

Andrea Y. Delgado Medrano

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

Travis Solley

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

Vancheswaran Gopalakrishnan

University of Texas at Houston - Department of Surgical Oncology

Beth Helmink

University of Texas at Houston - Department of Surgical Oncology

Rebecca J. Previs

University of Texas at Houston - Department of Gynecologic Oncology and Reproductive Medicine

Patricia J. Eifel

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

Anuja Jhingran

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

Lois M. Ramondetta

University of Texas at Houston - Department of Gynecologic Oncology and Reproductive Medicine

Andrew M. Futreal

University of Texas at Houston - Department of Genomic Medicine

Amir A. Jazaeri

University of Texas at Houston - Department of Gynecologic Oncology and Reproductive Medicine

Michael Frumovitz

University of Texas at Houston - Department of Gynecologic Oncology and Reproductive Medicine

Kathleen M. Schmeler

University of Texas at Houston - Department of Gynecologic Oncology and Reproductive Medicine

Robert T. Hillman

University of Texas at Houston - Department of Gynecologic Oncology and Reproductive Medicine

Geena Mathew

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

Jagannadha Sastry

University of Texas at Houston - Department of Immunology

Stephanie Dorta-Estremera

University of Texas at Houston - Department of Immunology

Aradhana Venkatesan

University of Texas at Houston - Department of Diagnostic Radiology

Diane Hutchinson

Baylor University - The Alkek Center for Metagenomics and Microbiome Research

Nadim J. Ajami

Baylor University - The Alkek Center for Metagenomics and Microbiome Research

Shane R. Stecklein

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

Cullen M. Taniguchi

University of Texas at Houston - Department of Experimental Radiation Oncology; University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

Pablo C. Okhuysen

University of Texas at Houston - Center for Infectious Diseases

Joseph F. Petrosino

Baylor University - The Alkek Center for Metagenomics and Microbiome Research

Jennifer Wargo

University of Texas at Houston - Department of Genomic Medicine

Stephen M. Hahn

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

Ann H. Klopp

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

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Abstract

Composition of the intestinal microbiome has been shown to impact generation of a tumor-specific immune response following chemotherapy and immune checkpoint blockade. We hypothesized that the local and intestinal microbiota may also impact immune activation and radiation response. We prospectively assessed the microbiota and T-cell repertoire of 30 cervical cancer patients throughout CRT. Greater diversity of the intestinal microbiome was associated with exceptional response and development of clonal T-cell expansion. Predominance of immunosuppressive Lactobacillus species in the cervix was associated with failure to expand clonal T-cells and decreased relapse-free survival. Patients with a robust response to CRT developed clonal expansion of T-cells, suggesting that highly radiation responsive cervical cancers generate an antigen specific immune response. Depletion of gut microbiome diversity and presence of vaginal Lactobacillus were associated with decreased presence of activated CD8 T-cell infiltration and decreased radiation response in an orthotopic model of HPV cancer, suggesting that microbial diversity is required for generation of effective antitumor immunity in radiation responsive HPV cancers.

Suggested Citation

Colbert, Lauren E. and Mikkelson, Megan and Medrano, Andrea Y. Delgado and Solley, Travis and Gopalakrishnan, Vancheswaran and Helmink, Beth and Previs, Rebecca J. and Eifel, Patricia J. and Jhingran, Anuja and Ramondetta, Lois M. and Futreal, Andrew M. and Jazaeri, Amir A. and Frumovitz, Michael and Schmeler, Kathleen M. and Hillman, Robert T. and Mathew, Geena and Sastry, Jagannadha and Dorta-Estremera, Stephanie and Venkatesan, Aradhana and Hutchinson, Diane and Ajami, Nadim J. and Stecklein, Shane R. and Taniguchi, Cullen M. and Okhuysen, Pablo C. and Petrosino, Joseph F. and Wargo, Jennifer and Hahn, Stephen M. and Klopp, Ann H., The Gut and Cervical Microbiome Promote Immune Activation and Response to Chemoradiation in Cervical Cancer (2018). Available at SSRN: https://ssrn.com/abstract=3199993 or http://dx.doi.org/10.2139/ssrn.3199993
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Lauren E. Colbert

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

1220 Holcombe Boulevard
Houston, TX 77030
United States

Megan Mikkelson

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

1220 Holcombe Boulevard
Houston, TX 77030
United States

Andrea Y. Delgado Medrano

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

1220 Holcombe Boulevard
Houston, TX 77030
United States

Travis Solley

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

1220 Holcombe Boulevard
Houston, TX 77030
United States

Vancheswaran Gopalakrishnan

University of Texas at Houston - Department of Surgical Oncology

1400 Pressler Drive
P.O. Box 301402
Houston, TX 77230-1402
United States

Beth Helmink

University of Texas at Houston - Department of Surgical Oncology

1400 Pressler Drive
P.O. Box 301402
Houston, TX 77230-1402
United States

Rebecca J. Previs

University of Texas at Houston - Department of Gynecologic Oncology and Reproductive Medicine

1515 Holocombe Blvd
Houston, TX 77030
United States

Patricia J. Eifel

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

1220 Holcombe Boulevard
Houston, TX 77030
United States

Anuja Jhingran

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

1220 Holcombe Boulevard
Houston, TX 77030
United States

Lois M. Ramondetta

University of Texas at Houston - Department of Gynecologic Oncology and Reproductive Medicine

1515 Holocombe Blvd
Houston, TX 77030
United States

Andrew M. Futreal

University of Texas at Houston - Department of Genomic Medicine

1515 Holocombe Blvd
Houston, TX 77030
United States

Amir A. Jazaeri

University of Texas at Houston - Department of Gynecologic Oncology and Reproductive Medicine

1515 Holocombe Blvd
Houston, TX 77030
United States

Michael Frumovitz

University of Texas at Houston - Department of Gynecologic Oncology and Reproductive Medicine

1515 Holocombe Blvd
Houston, TX 77030
United States

Kathleen M. Schmeler

University of Texas at Houston - Department of Gynecologic Oncology and Reproductive Medicine

1515 Holocombe Blvd
Houston, TX 77030
United States

Robert T. Hillman

University of Texas at Houston - Department of Gynecologic Oncology and Reproductive Medicine

1515 Holocombe Blvd
Houston, TX 77030
United States

Geena Mathew

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

1220 Holcombe Boulevard
Houston, TX 77030
United States

Jagannadha Sastry

University of Texas at Houston - Department of Immunology

1515 Holocombe Blvd
Houston, TX 77030
United States

Stephanie Dorta-Estremera

University of Texas at Houston - Department of Immunology

1515 Holocombe Blvd
Houston, TX 77030
United States

Aradhana Venkatesan

University of Texas at Houston - Department of Diagnostic Radiology

1515 Holocombe Blvd
Houston, TX 77030
United States

Diane Hutchinson

Baylor University - The Alkek Center for Metagenomics and Microbiome Research

6621 Fannin St
Houston, TX 77030
United States

Nadim J. Ajami

Baylor University - The Alkek Center for Metagenomics and Microbiome Research

6621 Fannin St
Houston, TX 77030
United States

Shane R. Stecklein

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

1220 Holcombe Boulevard
Houston, TX 77030
United States

Cullen M. Taniguchi

University of Texas at Houston - Department of Experimental Radiation Oncology ( email )

6565 MD Anderson Blvd, Unit 1052
Houston, TX 77030
United States

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

1220 Holcombe Boulevard
Houston, TX 77030
United States

Pablo C. Okhuysen

University of Texas at Houston - Center for Infectious Diseases

7000 Fannin, Suite 1800
Houston, TX 76013
United States

Joseph F. Petrosino

Baylor University - The Alkek Center for Metagenomics and Microbiome Research

6621 Fannin St
Houston, TX 77030
United States

Jennifer Wargo

University of Texas at Houston - Department of Genomic Medicine

1515 Holocombe Blvd
Houston, TX 77030
United States

Stephen M. Hahn

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology

1220 Holcombe Boulevard
Houston, TX 77030
United States

Ann H. Klopp (Contact Author)

University of Texas at Houston, Health Science Center at Houston (UTHealth), MD Anderson Cancer Center, Department of Radiation Oncology ( email )

1220 Holcombe Boulevard
Houston, TX 77030
United States

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