Extracellular Vesicle Mediated Tumor-Stromal Crosstalk Within an Engineered Lung Cancer Model

Kayla F. Goliwas; Hannah M. Ashraf; Anthony M. Wood; Yong Wang; Kenneth P. Hough; Sandeep Bodduluri; Mohammad Athar; Joel L. Berry; Selvarangan Ponnazhagan; Victor J. Thannickal; Jessy S. Deshane

doi:10.3389/fonc.2021.654922

Frontiers in Oncology (Apr 2021)

Extracellular Vesicle Mediated Tumor-Stromal Crosstalk Within an Engineered Lung Cancer Model

Kayla F. Goliwas,
Hannah M. Ashraf,
Anthony M. Wood,
Yong Wang,
Kenneth P. Hough,
Sandeep Bodduluri,
Mohammad Athar,
Joel L. Berry,
Selvarangan Ponnazhagan,
Victor J. Thannickal,
Jessy S. Deshane

Affiliations

Kayla F. Goliwas: Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
Hannah M. Ashraf: Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
Anthony M. Wood: Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
Yong Wang: Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
Kenneth P. Hough: Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
Sandeep Bodduluri: Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
Mohammad Athar: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, United States
Joel L. Berry: Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, United States
Selvarangan Ponnazhagan: Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, AL, United States
Victor J. Thannickal: Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
Jessy S. Deshane: Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, United States

DOI: https://doi.org/10.3389/fonc.2021.654922
Journal volume & issue: Vol. 11

Abstract

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Tumor-stromal interactions within the tumor microenvironment (TME) influence lung cancer progression and response to therapeutic interventions, yet traditional in vitro studies fail to replicate the complexity of these interactions. Herein, we developed three-dimensional (3D) lung tumor models that mimic the human TME and demonstrate tumor-stromal crosstalk mediated by extracellular vesicles (EVs). EVs released by tumor cells, independent of p53 status, and fibroblasts within the TME mediate immunomodulatory effects; specifically, monocyte/macrophage polarization to a tumor-promoting M2 phenotype within this 3D-TME. Additionally, immune checkpoint inhibition in a 3D model that included T cells showed an inhibition of tumor growth and reduced hypoxia within the TME. Thus, perfused 3D tumor models incorporating diverse cell types provide novel insights into EV-mediated tumor-immune interactions and immune-modulation for existing and emerging cancer therapies.

Published in Frontiers in Oncology

ISSN: 2234-943X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.frontiersin.org/journals/oncology/

About the journal

Abstract

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