The researchers, led by Dr. Katia Scotlandi, head of the Laboratory of Experimental Oncology at the IRCCS Orthopedic Institute Rizzoli, have identified an unprecedented function of the CD99 antigen. 

An antigen is a molecule that the immune system recognizes as foreign. In this case, the CD99 antigen is stimulated, through the recognition by specific antibodies, to induce the death of cancer cells. This can happen because CD99 determines the activation of so-called "eat me" signals and the inhibition of opposite signals, called "don’t eat me", on the surface of neoplastic cells. In turn, all this promotes the activity of phagocytosis by macrophages, cells of innate immunity able to engulf and neutralize cells and dangerous molecules. Since the CD99 antigen is also expressed on the same macrophages, the anti-CD99 antibodies also act on these cells, favoring the development of special M1 macrophages with anti-tumor characteristics. Overall, therefore, anti-CD99 antibodies attack the tumor on two fronts, acting both on cancer cells and on the tumor microenvironment, of which the macrophages are part. Among the most active antibodies is the human antibody C7, the use of which could have an important therapeutic potential against Ewing’s sarcoma and other cancer pathologies.

The study was conceived by researchers of the Laboratory of Experimental Oncology directed by Dr. Katia Scotlandi at the Rizzoli Orthopedic Institute. The research group of Dr. Gina Lisignoli of the Laboratory of Immunorheumatology and Tissue Regeneration has collaborated, which has made available its experience in the phenotypic characterization of macrophages, and the group of Dr. Francesca Salamanna, of Science and Surgical Technologies, as well as some researchers from the University of Bologna.

The results of the study, supported by the AIRC Foundation for Cancer Research, were recently published in the journal Cancer Immunology Research.