Immunomonitoring After Hematopoietic Stem Cell Transplantation

Overview

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option for many hematologic malignancies, in particular acute leukemias and myelodysplastic syndromes. At the center of these reactions are the donor's T and NK cells. Several studies have highlighted the impact of T cells reconstitution on post-transplant infection rates, relapse and GvHD. Most of the post-allogeneic immune reconstitution studies available to us today include young patients (\<60 years of age) who have had genoidentic or phenoidentic 10/10 allografts and mostly only study the phenotype of a limited number of immune cells. While it is important to know the absolute number reconstitution kinetics of the different categories of immune cells, it is essential to also be able to assess the function of the different cells. Knowledge of the restoration of T function at key dates after allogeneic stem cell transplantation would make it possible to adapt post allogeneic immunomodulation (immunosuppressive treatment and injections of donor lymphocytes) and anti-infectious prophylaxis for patients. The measurement of cytokine profiles after nonspecific stimulation of T and NK lymphocytes recently made available to the immunology laboratory of the CHU de Nice allows a routine assessment of T lymphocyte function (Th1, Th2 Th 17 and T regulatory) and NK by measurement of the secretion of different cytokines after stimulation of the patient's lymphocytes with different antigens (anti-CD3 and anti-TLR7). The cytokine profile during immune reconstitution in hematopoietic cell transplants has never been evaluated; we will analyze it with regard to clinical data: relapse, infections and GVHD.

Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative option for many hematologic malignancies, in particular acute leukemias and myelodysplastic syndromes. The success of the allogeneic transplant is based on the Graft versus Leukemia (GvL) effect which corresponds to the elimination of tumor cells by the donor's immune system from the recipient's body. Conversely, graft versus host disease (GvHD) is an immune response of the donor versus the host due to major and / or minor histocompatibility differences resulting in multi-organ damage and being the main cause of transplant-related mortality. The main causes of death in allogeneic patients are infections, relapse of the initial disease and GvHD. The relapse linked to an ineffectiveness of the anti-tumor response of the donor's immune system is responsible for 40% of transplant failures. GvHD is present in 40 to 70% of transplants. In both cases, therapeutic options are available in order to modulate the immune response. In fact, in the event of a relapse of the disease, reinjections of donor lymphocytes make it possible to trigger a GvL effect and cure. For patients with GvHD, on the other hand, treatment is based on increased immunosuppression. At the center of these reactions are the donor's T and NK cells. Several studies have highlighted the impact of T immune reconstitution on post-transplant infection rates, relapse and GvHD. Infections and relapses may be linked to insufficient antiviral or anti-tumor responses of the graft (Th1 pathway deficiency) while GvHD is linked to an excessive response of the graft against the host cells (Immune imbalance associating a excess of Th1, Th2 and Th17 responses). However, there is currently no routine test to predict the kinetics and quality of immune reconstitution in allogeneic patients. Most of the post-allogeneic immune reconstitution studies available to us today include young patients (\<60 years of age) who have had genoidentic or phenoidentic 10/10 allografts and mostly only study the phenotype of a limited number of immune cells. While it is important to know the absolute number reconstitution kinetics of the different categories of immune cells, it is essential to also be able to assess the function of the different cells. The evaluation of lymphocyte function is mainly based on the measurement of their ability to secrete different cytokines. This measure currently requires complex procedures exclusively reserved for research. Knowledge of the restoration of T function at key dates after allogeneic stem cell transplantation would make it possible to adapt post allogeneic immunomodulation (immunosuppressive treatment and injections of donor lymphocytes) and anti-infectious prophylaxis for patients. The measurement of cytokine profiles after nonspecific stimulation of T and NK lymphocytes recently made available to the immunology laboratory of the CHU de Nice allows a routine assessment of T lymphocyte function (Th1, Th2 Th 17 and T regulatory) and NK by measurement of the secretion of different cytokines after stimulation of the patient's lymphocytes with different antigens (anti-CD3 and anti-TLR7). The immunology laboratory of the Nice University Hospital recently demonstrated in a cohort of patients with a kidney transplant that the level of secretion of INF-γ (Th1 pathway) by T lymphocytes after non-specific stimulation was correlated with the risk of rejection and inversely correlated with the risk of infectious complications. In addition, in a cohort of patients with an autoimmune disease (Extra-Membranous Glomerulonephritis), the level of secretion of pro-inflammatory cytokines from the Th17 pathway (IL6, IL17, etc.) was correlated with the risk of thrombo-complications. embolic and relapse. The cytokine profile during immune reconstitution in hematopoietic cell transplants has never been evaluated; we will analyze it with regard to clinical data: relapse, infections and GVHD.