Joel LeMaoult (CEA, Paris), The immune checkpoint HLA-G: tolerogenic functions and their importance in cancer and transplantation.

HLA-G is a molecule that was first known to confer protection to the fetus from destruction by the immune system of its mother, thus critically contributing to fetal–maternal tolerance.

The first functional finding constituted the basis for HLA-G research and can be summarized as such: HLA-G, membrane-bound or soluble, strongly binds its inhibitory receptors on immune cells (NK, T, B, monocytes/dendritic cells), inhibits the functions of these effectors, and so induces immune inhibition. HLA-G function may therefore be beneficial because when expressed by a fetus or a transplant it protects them from rejection, or deleterious because when expressed by a tumor, it also protects it from antitumor immunity.

This is the primary HLA-G function: that of a checkpoint molecule.

This presentation will summarize the work that has been done in the past years to characterize HLA-G itself, its regulation, its functions and mechanisms of action, and its pathological relevance; it will also place a special emphasis on the clinical uses of a molecule such as HLA-G, with a focus on cancer and transplantation.