SOD3 boosts T cell infiltration by normalizing the tumor endothelium and inducing laminin-α4

Oncoimmunology. 2020 Jul 12;9(1):1794163. doi: 10.1080/2162402X.2020.1794163.

Abstract

The conversion of a non-T cell-inflamed into a T cell-inflamed tumor microenvironment (TME) is a key to sensitizing tumors to T-cell-based immunotherapies. Recent data show that the extracellular superoxide dismutase (SOD3) alters endothelial basement membrane (EC-BM) composition, providing permissive signals that enhance tumor infiltration by effector T cells.

Abbreviations: AJ, adherens junction; EC, endothelial cell; EC-BM, endothelial basement membrane; HIF, hypoxia-inducible factor; ICAM-1, intercellular adhesion molecule-1; LAMA4, laminin-α4; SOD3, superoxide dismutase-3; TME, tumor microenvironment; VCAM-1, vascular cell adhesion molecule-1; VEGF, vascular-endothelial growth factor.

Keywords: Oxidative stress; TIL; adoptive cell transfer; diapedesis; endothelium; extracellular matrix; immunotherapy; laminin; normalization; tumor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Endothelium, Vascular
  • Humans
  • Laminin*
  • Neoplasms*
  • Superoxide Dismutase / genetics
  • T-Lymphocytes
  • Tumor Microenvironment

Substances

  • Laminin
  • SOD3 protein, human
  • Superoxide Dismutase

Grants and funding

This work was funded by the Ministry of Economy and Competitiveness (SAF2017-83732-R; AEI/FEDER, EU) and the Comunidad de Madrid (B2017/BMD-3733; Immunothercan-CM). DM-R is a recipient of a predoctoral fellowship from the Spanish Ministry of Science, Innovation and Universities, and the EU Social Fund (PRE2018-084023).