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

Blood. 2022 Sep 15;140(11):1305-1321. doi: 10.1182/blood.2022015522.


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.

MeSH terms

  • CD4-Positive T-Lymphocytes / pathology
  • Cross-Sectional Studies
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Myeloid, Acute* / pathology
  • Leukemia, Myeloid, Acute* / therapy
  • Ligands
  • Receptors, Immunologic
  • Recurrence
  • Transplantation, Homologous


  • Ligands
  • Receptors, Immunologic
  • TIGIT protein, human