Correlation between the recovery of certain innate immune lymphoid cells and the occurrence of GvHD after hematopoietic stem cell transplantation.

Innate lymphoid cell recovery and occurrence of GvHD after hematopoietic stem cell transplantation.

Piperoglou C, Larid G, Vallentin B, et al. Innate lymphoid cell recovery and occurrence of GvHD after hematopoietic stem cell transplantation. J Leukoc Biol. 2021;1–12.

By using biological resources of cohorts of adult and pediatric patients treated with bone marrow transplants, two teams from the Timone Hospital, the Hematology and Pediatric Oncology Department and Marseille Immunopôle managed to establish a correlation between the reconstitution of a certain population of immune cells, innate lymphoid cells (ILCs), the level of protection of certain epithelial tissues and the occurrence of acute or chronic graft-versus-host disease (GvHD).

With nearly 24,000 patients treated every year in Europe, of which 2,000 are in France and 15% are children, allogeneic hematopoietic stem cell transplantation (HSCT) represents the last therapeutic line in the management of severe hematological diseases (leukemia, lymphoma, etc.) or immunodeficiencies. While interest in HSCT is largely recognized by the international scientific community, this therapeutic protocol does not however come without risks for the 50% of patients who suffer, in the short- or medium-term, from infectious, pulmonary, cardiac or dermatological complications that can be severe and all too often fatal in 25% of cases. GvHD is the most frequent complication after allogeneic HSCT. In this disease, immune cells from the donor present in the graft perceive the host to be a foreign body and attack their healthy organs.

There are two forms of GvHD: acute GvHD, which generally occurs in the first few months following transplantation and affects the skin, liver and digestive tract; and chronic GvHD, which appears later and can affect all organs in a cutaneous, buccal, ocular, pulmonary or muscular-articulatory form. To date, it is not possible to predict the occurrence of these complications and the resources to treat them remain limited.

Timing of post-transplant recovery of ILCs close to adaptive immunity cells

Innate lymphoid cells are the most recently identified members of the lymphocyte family (Nat Rev Immunol. 2010 Sep; 10(9):664-74). Split into various subgroups, they have the morphology of a lymphoid cell, produce the same cocktails of cytokines as T-helper lymphocytes but, just like their innate immune congeners, they lack antigen-specific receptors. Another difference that characterizes them is that unlike natural killer (NK) cells, and B- and T-lymphocytes found in significant quantities in peripheral blood, ILCs are mainly found in mucosa.

By drawing on work published in 2016 (Nat Immunol. 2016;17:1291–1299) that described the normal values of ILCs circulating in healthy adult and pediatric subjects, the researchers led a comparative study on the recovery of these populations (ILC1, 2 and 3) after allogeneic HSCT. The results obtained concerning the timing of post-transplant recovery are comparable to those observed previously for adaptive immunity T-cells, but differ to a very large extent from recovery curves for cytotoxic ILCs (NK cells, known for their anti-tumoral and anti-viral activity).

Correlation between the recovery of ILCs, the level of epithelium protection of patients and the occurrence of acute and chronic GvHD

By drawing on biological resources of adult and pediatric patients respectively, made available by the retrospective cohort CRYOSTEM, and obtained thanks to the support of the Laurette Fugain Association, researchers were able to measure the presence of progenitors of ILCs in the blood that expressed specific activation markers. Known for their role in the protection and regeneration of epithelia, certain populations of ILCs were found in a significant concentration in transplanted patients who did not develop acute or chronic GvHD. Conversely, in those who developed severe acute GvHD, the concentrations of ILCs remained weak.

This study also showed that this correlation between the presence of certain ILCs and the occurrence of acute and chronic GvHD, already described in a previous publication (Blood. 2014 Jul 31;124(5):812-21), concerning patients treated by allogeneic HSCT for acute leukemia, is reproducible and independent of the hematological disease that led to allogeneic HSCT. This is a major point that seems to indicate to researchers that the markers used in this study and expressed by these circulating ILCs are robust and reliable.