Immune landscape after allo-HSCT: TIGIT- and CD161-expressing CD4 T cells are associated with subsequent leukemia relapse.

Autor:	Gournay V; Human Immunology, Pathophysiology and Immunotherapy, INSERM UMR-976, Paris, France.; Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France.; Hématologie/Transplantation, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France., Vallet N; Human Immunology, Pathophysiology and Immunotherapy, INSERM UMR-976, Paris, France.; Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France., Peux V; Human Immunology, Pathophysiology and Immunotherapy, INSERM UMR-976, Paris, France.; Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France., Vera K; Human Immunology, Pathophysiology and Immunotherapy, INSERM UMR-976, Paris, France.; Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France., Bordenave J; Human Immunology, Pathophysiology and Immunotherapy, INSERM UMR-976, Paris, France.; Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France., Lambert M; Human Immunology, Pathophysiology and Immunotherapy, INSERM UMR-976, Paris, France.; Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France., Corneau A; UMS037 PASS, Plateforme de Cytométrie CyPS, Faculté des Sciences, Sorbonne-Université, Paris, France; and., Michonneau D; Human Immunology, Pathophysiology and Immunotherapy, INSERM UMR-976, Paris, France.; Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France.; Hématologie/Transplantation, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France., Peffault de Latour R; Hématologie/Transplantation, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France., Caillat-Zucman S; Human Immunology, Pathophysiology and Immunotherapy, INSERM UMR-976, Paris, France.; Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France.; Laboratoire d'Immunologie, Hôpital Saint-Louis, AP-HP, Paris, France., Socié G; Human Immunology, Pathophysiology and Immunotherapy, INSERM UMR-976, Paris, France.; Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France.; Hématologie/Transplantation, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France., Chevalier MF; Human Immunology, Pathophysiology and Immunotherapy, INSERM UMR-976, Paris, France.; Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2022 Sep 15; Vol. 140 (11), pp. 1305-1321.
DOI:	10.1182/blood.2022015522
Abstrakt:	Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective treatment for selected patients with acute myeloid leukemia (AML) and relies on a "graft-versus-leukemia" effect (GVL) where donor T lymphocytes mediate control of malignant cell growth. However, relapse remains the major cause of death after allo-HSCT. In various malignancies, several immunoregulatory mechanisms have been shown to restrain antitumor immunity, including ligand-mediated engagement of inhibitory receptors (IRs) on effector cells, and induction of immunosuppressive cell subsets, such as regulatory T cells (Tregs) or myeloid-derived suppressor cells (MDSCs). Relapse after HSCT remains a major therapeutic challenge, but immunoregulatory mechanisms involved in restraining the GVL effect must be better deciphered in humans. We used mass cytometry to comprehensively characterize circulating leukocytes in 2 cohorts of patients after allo-HSCT. We first longitudinally assessed various immunoregulatory parameters highlighting specific trends, such as opposite dynamics between MDSCs and Tregs. More generally, the immune landscape was stable from months 3 to 6, whereas many variations occurred from months 6 to 12 after HSCT. Comparison with healthy individuals revealed that profound alterations in the immune equilibrium persisted 1 year after HSCT. Importantly, we found that high levels of TIGIT and CD161 expression on CD4 T cells at month 3 after HSCT were distinct features significantly associated with subsequent AML relapse in a second cross-sectional cohort. Altogether, these data provide global insights into the reconstitution of the immunoregulatory landscape after HSCT and highlight non-canonical IRs associated with relapse, which could open the path to new prognostic tools or therapeutic targets to restore subverted anti-AML immunity. (© 2022 by The American Society of Hematology.)
Databáze:	MEDLINE
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