Skip to Main content Skip to Navigation
New interface
Journal articles

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

Abstract : 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 on effector cells, and induction of immunosuppressive cell-subsets such as regulatory T cells (Tregs) or myeloid-derived suppressor cells (MDSCs). While relapse after HSCT remains a major therapeutic challenge, immunoregulatory mechanisms involved in restraining the GVL effect need to be better deciphered in humans. We used mass cytometry to comprehensively characterize circulating leukocytes in two 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 rather stable from month-3 to 6, while many variations occurred from month-6 to 12 post-HSCT. Comparison with healthy individuals revealed that profound alterations in the immune equilibrium persisted 1-year post-HSCT. Importantly, we found that high levels of TIGIT and CD161 expression on CD4 T cells at month 3 post-HSCT were distinct features significantly associated with subsequent AML relapse in a second cross sectional cohort. Altogether, these data provide global insights into the immunoregulatory landscape reconstitution following HSCT, and highlight non-canonical inhibitory receptors associated with relapse, which could open the path towards new prognostic tools or therapeutic targets to restore subverted anti-AML immunity.
Complete list of metadata

https://hal.sorbonne-universite.fr/hal-03747377
Contributor : Nadège BRUNEL Connect in order to contact the contributor
Submitted on : Monday, August 8, 2022 - 11:02:47 AM
Last modification on : Thursday, September 1, 2022 - 4:08:10 AM
Long-term archiving on: : Wednesday, November 9, 2022 - 6:16:07 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : 2023-01-12

Please log in to resquest access to the document

Identifiers

Citation

Viviane Gournay, Nicolas Vallet, Vivien Peux, Kristi Vera, Jennifer Bordenave, et al.. Immune landscape after allo-HSCT: TIGIT and CD161-expressing CD4 T cells are associated with subsequent leukemia relapse. Blood, In press, ⟨10.1182/blood.2022015522⟩. ⟨hal-03747377⟩

Share

Metrics

Record views

57