The Hemato-Immunology Research Service (SRHI), created in 1991 by Prof. Edgardo D. Carosella following the Chernobyl accident, is dedicated to studying the mechanisms of immune tolerance in transplants, as well as the immunological mechanisms of tumor escape from host surveillance. The work carried out by the SRHI since 1992 has led to the discovery of the immune tolerance function of the non-classical HLA class I molecule, HLA-G. The SRHI, which has established itself as an international leader in this field, brings together numerous laboratories from several countries and organizes international conferences and workshops on HLA-G.

Based on its initial demonstration of the fundamental role of HLA-G in feto-maternal tolerance, a perfect physiological example of successful allogeneic transplant tolerance, the SRHI team then transposed its observations to solid organ transplantation, based on the principle that HLA-G contributes to allograft acceptance. At the same time, the SRHI has developed oncology studies based on the deleterious effects of immune tolerance, with the HLA-G molecule acting as an immune checkpoint and allowing the tumor to escape antitumor immune responses.

In the 1990s, the SRHI team was the first to demonstrate the immunotolerant function of the HLA-G molecule and its fundamental role in feto-maternal tolerance. Indeed, the expression of HLA-G by the fertilized egg is essential for embryo implantation and proper development. Since fetomaternal tolerance is a unique example of successful allogeneic tissue tolerance, the team hypothesized that HLA-G could also induce a state of tolerance in transplants. The team first demonstrated the expression of soluble and membrane HLA-G by allografts, then showed that HLA-G exerts its tolerogenic function by acting at all levels of the allogeneic reaction. HLA-G inhibits the cytolytic function of NK cells, the antigen-specific cytolytic function of cytotoxic T lymphocytes (CTLs), the alloproliferative response of CD4+ T cells, the antibody production by B cells, and the maturation and function of dendritic cells. The SRHI has also demonstrated that HLA-G induces regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). This work has positioned HLA-G as a major molecule in immune checkpoints, with broad immunoregulatory functions that affect both innate and adaptive immunity through its interaction with the inhibitory receptors ILT2 and ILT4 (LILRB1/CD85j and LILRB2/CD85d), which are differentially expressed by immune cells. Thus, unlike the CTLA-4/B7 and PD1/PD-L1 checkpoints, the ILT/HLA-G checkpoint inhibits all actors and blocks all stages of the immune response, from the activation of antigen-presenting cells (APCs) to the functioning of cytotoxic T lymphocytes (CTLs) or activated NK cells.

Since 2000, the SRHI team has also conducted studies in oncology, a pathological context in which immune responses directed against tumors are compromised. First, the team demonstrated that although HLA-G is mainly expressed by fetal cells and not by adult tissues, this molecule was neo-expressed to varying degrees by most tumors. In this context, the SRHI team demonstrated that HLA-G exerted its immune checkpoint inhibitory function and inhibited antitumor responses, thereby causing tumor escape from immunosurveillance

In order to develop translational studies in onco-uro-immunology, a translational group under the responsibility of Prof. Desgrandchamps was created in 2013 within the SRHI. This clinical group includes teams from Saint-Louis Hospital: urology (Prof. F. Desgrandchamps), medical oncology (Prof. S. Culine), radiotherapy (Prof. C. Hennequin), interventional radiology (Prof. E. de Kerviler), and pathological anatomy (Dr. J. Verine).