A dhesion analysis via a tumor vasculature-like microfluidic device identifies CD8+ T cells with enhanced tumor homing to improve cell therapy
Camila P. Camargo,
Abir K. Muhuri,
Yunus Alapan,
Lauren F. Sestito,
Megha Khosla,
Margaret P. Manspeaker,
Aubrey S. Smith,
Chrystal M. Paulos,
Susan N. Thomas
Affiliations
Camila P. Camargo
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA
Abir K. Muhuri
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA
Yunus Alapan
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA
Lauren F. Sestito
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA
Megha Khosla
School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
Margaret P. Manspeaker
Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA; School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA
Aubrey S. Smith
Winship Cancer Institute, Emory University, Atlanta, GA 30332, USA; Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, SC 29425, USA
Chrystal M. Paulos
Winship Cancer Institute, Emory University, Atlanta, GA 30332, USA
Susan N. Thomas
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA; Winship Cancer Institute, Emory University, Atlanta, GA 30332, USA; Corresponding author
Summary: CD8+ T cell recruitment to the tumor microenvironment is critical for the success of adoptive cell therapy (ACT). Unfortunately, only a small fraction of transferred cells home to solid tumors. Adhesive ligand-receptor interactions have been implicated in CD8+ T cell homing; however, there is a lack of understanding of how CD8+ T cells interact with tumor vasculature-expressed adhesive ligands under the influence of hemodynamic flow. Here, the capacity of CD8+ T cells to home to melanomas is modeled ex vivo using an engineered microfluidic device that recapitulates the hemodynamic microenvironment of the tumor vasculature. Adoptively transferred CD8+ T cells with enhanced adhesion in flow in vitro and tumor homing in vivo improve tumor control by ACT in combination with immune checkpoint blockade. These results show that engineered microfluidic devices can model the microenvironment of the tumor vasculature to identify subsets of T cells with enhanced tumor infiltrating capabilities, a key limitation in ACT.
