Adhesion 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

doi:10.1016/j.celrep.2023.112175

Adhesion analysis via a tumor vasculature-like microfluidic device identifies CD8⁺ T cells with enhanced tumor homing to improve cell therapy

Cell Rep. 2023 Mar 28;42(3):112175. doi: 10.1016/j.celrep.2023.112175. Epub 2023 Feb 26.

Authors

Camila P Camargo¹, Abir K Muhuri¹, Yunus Alapan¹, Lauren F Sestito², Megha Khosla³, Margaret P Manspeaker⁴, Aubrey S Smith⁵, Chrystal M Paulos⁶, Susan N Thomas⁷

Affiliations

¹ 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.
² Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
³ School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
⁴ 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.
⁵ Winship Cancer Institute, Emory University, Atlanta, GA 30332, USA; Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
⁶ Winship Cancer Institute, Emory University, Atlanta, GA 30332, USA.
⁷ 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. Electronic address: susan.thomas@gatech.edu.

Abstract

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.

Keywords: CP: Cancer; CP: Immunology; cancer immunotherapy; cell adhesion; lymphocyte; microfluidic system.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

CD8-Positive T-Lymphocytes*
Cell- and Tissue-Based Therapy
Humans
Lymphocytes, Tumor-Infiltrating
Melanoma* / metabolism
Melanoma* / therapy
Tumor Microenvironment

Abstract

Publication types

MeSH terms

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