Extracellular Vesicle Mediated Tumor-Stromal Crosstalk Within an Engineered Lung Cancer Model
Year: 2021
Type: article
Abstract: Tumor-stromal interactions within the tumor microenvironment (TME) influence lung cancer progression and response to therapeutic interventions, yet traditionalin vitrostudies 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.
Source: Frontiers in Oncology
Institution: University of Alabama at Birmingham
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Awards: Lumina III System for UAB Optical Imaging, G3301274224, G5674799911, G591701811, Rheumatic Diseases Core Centers (P30), Therapeutic Targeting of the Myofibroblast in Fibrotic Lung Disease, G9000059695, G9000075556, G9000169993, G9000212593, G9000315146, Comprehensive Cancer Center Support Grant, Training Program in Lung Biology and Translational Medicine
OpenAlex ID: W3161662654