Endothelial cell anergy

Vasculature-based immune suppression mechanisms. Tumor endothelial cell anergy is represented by the suppression of endothelial adhesion molecules, such as ICAM-1, VCAM-1 and E-selectin. The tumor vasculature contributes to more immune suppression through enhanced expression of immune checkpoint molecules, such as PD-L1 and IDO, that suppress the function of leukocytes. In addition, the tumor vasculature expresses molecules, such as FASL and galectin-1, that can give death signals to leukocytes.[1]

Endothelial cell anergy is a condition during the process of angiogenesis,[2] where endothelial cells, the cells that line the inside of blood vessels, can no longer respond to inflammatory cytokines.[3][4] These cytokines are necessary to induce the expression of cell adhesion molecules to allow leukocyte infiltration from the blood into the tissue at places of inflammation, such as a tumor. This condition, which protects the tumor from the immune system, is the result of exposure to angiogenic growth factors.

Next to endothelial cell anergy, there are more vascular mechanisms that contribute to escape from immunity, such as the expression of immune checkpoint molecules (e.g. PD-L1/2) and proteins that can deliver death signals in leukocytes (Fas ligand and galectin-1).

  1. ^ Huinen ZR, Huijbers EJ, van Beijnum JR, Nowak-Sliwinska P, Griffioen AW (August 2021). "Anti-angiogenic agents - overcoming tumour endothelial cell anergy and improving immunotherapy outcomes". Nature Reviews. Clinical Oncology. 18 (8): 527–540. doi:10.1038/s41571-021-00496-y. PMID 33833434. S2CID 233187995.
  2. ^ Dudley AC, Griffioen AW (April 2023). "Pathological angiogenesis: mechanisms and therapeutic strategies". Angiogenesis. 26 (3): 313–347. doi:10.1007/s10456-023-09876-7. PMC 10105163. PMID 37060495.
  3. ^ Griffioen AW, Damen CA, Martinotti S, Blijham GH, Groenewegen G (March 1996). "Endothelial intercellular adhesion molecule-1 expression is suppressed in human malignancies: the role of angiogenic factors". Cancer Research. 56 (5): 1111–1117. PMID 8640769.
  4. ^ Griffioen AW, Damen CA, Blijham GH, Groenewegen G (July 1996). "Tumor angiogenesis is accompanied by a decreased inflammatory response of tumor-associated endothelium". Blood. 88 (2): 667–673. doi:10.1182/blood.V88.2.667.bloodjournal882667. PMID 8695814. S2CID 35620015.