In a recent study published in Cell , a group of researchers elucidated the shared immune tolerance mechanisms in cancer and pregnancy, focusing on the role of progestogen-induced B7 Homolog 4 (B7-H4) (an immune checkpoint protein) as an onco-fetal immune tolerance checkpoint (mechanisms allowing the immune coexistence of cancer and fetal cells). Immune checkpoint blockade (ICB) elicits durable responses across various cancers; however, most patients do not respond to current immunotherapy due to key immune-regulatory mechanisms fostering suppressive networks in the tumor microenvironment (TME). This leads to cancer immune evasion and resistance to ICB.
Pregnancy, an ideal model for exploring immune tolerance, shares critical immunosuppressive pathways with cancer, including Programmed Death-Ligand 1 (PD-L1), Human Leukocyte Antigen -G (HLA-G), Indoleamine 2,3-Dioxygenase (IDO), and Tregs. Further research is needed to fully understand the mechanisms and therapeutic potential of targeting B7-H4 in cancer and pregnancy-related immune tolerance. In the animal studies, a spontaneous tumor model was induced using Medroxyprogesterone Acetate (MPA) and 7,12-Dimethylbenz[a]anthracene (DMBA).
Age-matched female Wild Type (WT) and B7-H4−/− mice were implanted with a pellet containing slow-releasing MPA subcutaneously. Mice were administered 1 mg of DMBA weekly by oral gavage for six doses. Tumor growth was monitored, and evaluable tumor numbers were recorded.
Tumor dimensions were.
