Integrin subunit alpha M (CD11b) (ITGAM)

Integrin subunit alpha M, commonly known as CD11b, is a transmembrane protein that forms the heterodimeric Mac-1 (or CR3) complex with the beta-2 subunit (CD18). It is predominantly expressed on the surface of myeloid-lineage cells, including macrophages, neutrophils, and myeloid-derived suppressor cells (MDSCs), where it plays an essential role in mediating leukocyte adhesion, transendothelial migration, and the phagocytosis of complement-opsonized pathogens. In the context of oncology, CD11b+ cells frequently infiltrate the tumor microenvironment to exert immunosuppressive effects that hinder T-cell activity and promote angiogenesis. Therapeutic strategies targeting CD11b often employ small-molecule agonists, such as GB1275, which allosterically stabilize the receptor in an active conformation. This activation paradoxically reduces the recruitment of immunosuppressive myeloid cells into tumors and triggers the repolarization of existing tumor-associated macrophages into an anti-tumor, pro-inflammatory state. Clinical development has focused on combining these CD11b modulators with immune checkpoint inhibitors to treat advanced solid tumors, including pancreatic and prostate cancers.

Other names

CD11BMAC-1 subunit alphaComplement receptor 3 alpha subunitCR3AMO1AIntegrin alpha M

Small-molecule agonism or positive allosteric modulation that stabilizes the high-affinity conformation of the CD11b/CD18 heterodimer, leading to increased myeloid cell adhesion to the vascular endothelium (thereby inhibiting extravasation into tissues) and promoting the repolarization of immunosuppressive macrophages toward a pro-inflammatory M1-like phenotype.