Studying TCR T cell anti-tumor activity in a microfluidic intrahepatic tumor model

Methods Cell Biol. 2018:146:199-214. doi: 10.1016/bs.mcb.2018.05.009. Epub 2018 Jul 12.

Abstract

Adoptive cell therapy (ACT) is showing promising results in clinical trials but many challenges remain in understanding the key role of the tumor microenvironment. These challenges constitute a major barrier to advancing the field. Therefore, it is crucial to perform preclinical tests of the developed ACT strategies in a fast and reproducible way to assess the potential for patient therapy. Here, we describe the development of an intrahepatic tumor model in a microfluidic device for screening T cell-based immunotherapeutic strategies and the role of monocytes in these therapies. This system can be used to test also the effects of supporting cytokine administration and changes in oxygen level that are typically found in a liver tumor microenvironment. As a result, these 3D microfluidic assays provide a means to quantify T cell anti-tumor activity under different conditions to optimize existing therapeutic strategies or the design of new ones.

Keywords: 3D cell culture; Adoptive cell therapy; Cancer; Immunotherapy; Microfluidics; Monocytes; T cells; Tumor microenvironment; Tumor model.

Publication types

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

MeSH terms

  • Animals
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / pathology*
  • Microfluidics / methods*
  • Models, Biological*
  • Rats
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocytes / metabolism*
  • Tumor Microenvironment

Substances

  • Receptors, Antigen, T-Cell