ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis

J Leukoc Biol. 2020 Sep;108(3):787-799. doi: 10.1002/JLB.2MR0220-549R. Epub 2020 Mar 17.


ICAM-1 is a cell surface glycoprotein and an adhesion receptor that is best known for regulating leukocyte recruitment from circulation to sites of inflammation. However, in addition to vascular endothelial cells, ICAM-1 expression is also robustly induced on epithelial and immune cells in response to inflammatory stimulation. Importantly, ICAM-1 serves as a biosensor to transduce outside-in-signaling via association of its cytoplasmic domain with the actin cytoskeleton following ligand engagement of the extracellular domain. Thus, ICAM-1 has emerged as a master regulator of many essential cellular functions both at the onset and at the resolution of pathologic conditions. Because the role of ICAM-1 in driving inflammatory responses is well recognized, this review will mainly focus on newly emerging roles of ICAM-1 in epithelial injury-resolution responses, as well as immune cell effector function in inflammation and tumorigenesis. ICAM-1 has been of clinical and therapeutic interest for some time now; however, several attempts at inhibiting its function to improve injury resolution have failed. Perhaps, better understanding of its beneficial roles in resolution of inflammation or its emerging function in tumorigenesis will spark new interest in revisiting the clinical value of ICAM-1 as a potential therapeutic target.

Keywords: Inflammation; adhesion molecules; immune cells; metastasis; migration; tumorigenesis; wound healing.

Publication types

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

MeSH terms

  • Alternative Splicing
  • Animals
  • Biomarkers
  • Carcinogenesis*
  • Chemotaxis, Leukocyte / physiology
  • Endothelium, Vascular / physiology
  • Epithelium / physiology
  • Humans
  • Inflammation / blood
  • Inflammation / physiopathology*
  • Intercellular Adhesion Molecule-1 / blood
  • Intercellular Adhesion Molecule-1 / chemistry
  • Intercellular Adhesion Molecule-1 / physiology*
  • Mice
  • Neoplasm Metastasis
  • Neoplastic Stem Cells / cytology
  • Phosphorylation
  • Prognosis
  • Protein Processing, Post-Translational
  • Stem Cell Niche
  • Wound Healing / physiology*


  • Biomarkers
  • Intercellular Adhesion Molecule-1