Bone marrow central memory and memory stem T-cell exhaustion in AML patients relapsing after HSCT.
other · Level V
Where this comes from
- Record sourced from PubMed, PMID 30911002.
- Also identified by DOI 10.1038/s41467-019-08871-1 and PMC identifier 6434052.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The major cause of death after allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for acute myeloid leukemia (AML) is disease relapse. We investigated the expression of Inhibitory Receptors (IR; PD-1/CTLA-4/TIM-3/LAG-3/2B4/KLRG1/GITR) on T cells infiltrating the bone marrow (BM) of 32 AML patients relapsing (median 251 days) or maintaining complete remission (CR; median 1 year) after HSCT. A higher proportion of early-differentiated Memory Stem (T<sub>SCM</sub>) and Central Memory BM-T cells express multiple IR in relapsing patients than in CR patients. Exhausted BM-T cells at relapse display a restricted TCR repertoire, impaired effector functions and leukemia-reactive specificities. In 57 patients, early detection of severely exhausted (PD-1<sup>+</sup>Eomes<sup>+</sup>T-bet<sup>-</sup>) BM-T<sub>SCM</sub> predicts relapse. Accordingly, leukemia-specific T cells in patients prone to relapse display exhaustion markers, absent in patients maintaining long-term CR. These results highlight a wide, though reversible, immunological dysfunction in the BM of AML patients relapsing after HSCT and suggest new therapeutic opportunities for the disease.
Medical subject headings
- Clonal Anergy
- Gene Expression Regulation, Leukemic
- Hematopoietic Stem Cell Transplantation
- Immunologic Memory
- Leukemia, Myeloid, Acute
- T-Lymphocytes