Tumors resurrect an embryonic vascular program to escape immunity

Sci Immunol. 2022 Jan 14;7(67):eabm6388. doi: 10.1126/sciimmunol.abm6388. Epub 2022 Jan 14.

Abstract

Tumors can escape immunity through multiple mechanisms, one of which is by enforcing a state of unresponsiveness of the tumor vasculature to inflammatory cytokines. This results in a lack of adhesiveness of angiogenic endothelial cells for immune cells and thus compromised immunity. This type of escape from immunity, called tumor endothelial cell anergy, is the result of exposure to angiogenic growth factors. Angiogenesis is a hallmark not only of cancer but also of embryonic development. It is assumed that angiogenesis-induced suppression of adhesion molecules is a regulatory function to provide an embryo with immune privileged conditions and allow uninterrupted growth and development. It is becoming clear that similar conditions are used by tumors to evade the immune system and ensure progressive growth. Gaining enhanced insight into these immune-privileged conditions is important as endothelial cell anergy can be overcome by angiogenesis inhibitors, an application that is rapidly emerging as a successful strategy to improve immunotherapy. The literature on endothelial adhesion molecule expression and leukocyte-vessel wall interactions during embryonic and fetal development is sparse, but available data allow the hypothesis that tumors, through angiogenesis, enforce an embryonic-like gene expression program in endothelial cells to suppress leukocyte infiltration and compromise antitumor immunity.

Publication types

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

MeSH terms

  • Animals
  • Endothelial Cells / immunology*
  • Humans
  • Immunotherapy
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • Neovascularization, Pathologic / immunology*
  • Neovascularization, Pathologic / therapy