CD47 is a cell surface glycoprotein with a variety of functions including regulation of phagocytosis through binding to the macrophage and dendritic cell specific protein signal regulatory protein alpha (SIRP alpha). Binding of SIRP alpha to CD47, as SIRP alpha & CD47 immune checkpoint pathway, essentially sends a 'don't eat me' message to macrophages by initiating signaling to inhibit phagocytosis. Increased expression of CD47 is proposed to be a mechanism through which cancer cells evade immune detection and phagocytosis. CD47 expression is increased in several cancer types including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), primary effusion lymphoma, multiple myeloma, leiomyosarcoma, and bladder cancer, and targeting of CD47 on cancer cells with an anti-CD47 blocking antibody can promote phagocytosis by macrophages in vitro. Further, treatment with an anti-CD47 blocking antibody synergized with rituximab treatment to promote phagocytosis in vitro and to eliminate cancer cells in an in vivo xenograft model of non-Hodgkin lymphoma. Further results demonstrate that CD47 expression increases in a variety of human solid tumor types and that blocking the SIRP alpha & CD47 immune checkpoint pathway with an anti-CD47 antibody can promote phagocytosis of solid tumor cells in vitro and reduce growth of solid tumors in vivo.
Martina Seiffert et al. Signal-regulatory protein α (SIRPα) but not SIRPβ is involved in T-cell activation, binds to CD47 with high affinity, and is expressed on immature CD34+CD38−hematopoietic cells. 2001; Blood: 97 (9).
|Co-inhibitory immune checkpoint pathways||Co-stimulatory immune checkpoint pathways|
|PD1 & PD-L1 immune checkpoint pathway||CD40 & CD40L immune checkpoint pathway|
|CTLA-4 & CD80 (CD86) immune checkpoint pathway||OX40 & OX40L immune checkpoint pathway|
|B7-H3 / CD276 immune checkpoint pathway||HVEM & LIGHT immune checkpoint pathway|
|B7-H4 / B7S1 / B7x immune checkpoint pathway||CD28 & CD80 (CD86) immune checkpoint pathway|
|HVEM & BTLA immune checkpoint pathway||GITR & GITR Ligand immune checkpoint pathway|
|HVEM & CD160 immune checkpoint pathway||CD27 & CD70 immune checkpoint pathway|
|LAG3 / CD223 / Lymphocyte activation gene 3 immune checkpoint pathway||4-1BB & 4-1BBL immune checkpoint pathway|
|Galectin-9 & TIM-3 immune checkpoint pathway||ICOS & ICOS Ligand immune checkpoint pathway|
|Indoleamine 2,3-dioxygenase/IDO immune checkpoint pathway||CD266 & CD155 immune checkpoint pathway|
|VISTA / B7-H5 / GI24 immune checkpoint pathway|
|CEACAM1 / CD66a immune checkpoint pathway|
|2B4 & CD48 immune checkpoint pathway|
|TIGIT & CD155 immune checkpoint pathway|