CD8+ T cells expand stem and progenitor cells in favorable but not adverse risk acute myeloid leukemia.

Radpour, Ramin; Riether, Carsten; Simillion, Cedric; Höpner, Sabine; Bruggmann, Rémy; Ochsenbein, Adrian (2019). CD8+ T cells expand stem and progenitor cells in favorable but not adverse risk acute myeloid leukemia. Leukemia, 33(10), pp. 2379-2392. Nature Publishing Group 10.1038/s41375-019-0441-9

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CD8+ T cell immunosurveillance is crucial in solid tumors and T cell dysfunction leads to tumor progression. In contrast, the role of CD8+ T cells in the control of leukemia is less clear. We characterized the molecular signature of leukemia stem/progenitor cells (LSPCs) and paired CD8+ T cells in patients with acute myeloid leukemia (AML). Epigenetic alterations via histone deacetylation reduced the expression of immune-related genes in bone marrow (BM)-infiltrating CD8+ T cells. Surprisingly, a silenced gene expression pattern in CD8+ T cells significantly correlated with an improved prognosis. To define interactions between CD8+ T cells and LSPCs, we performed comprehensive correlative network modeling. This analysis indicated that CD8+ T cells contribute to the maintenance/expansion of LSPCs, particularly in favorable risk AML. Functionally, CD8+ T cells in favorable AML induced the expansion of LSPCs by stimulating the autocrine production of important hematopoietic cytokines such as interleukin (IL)-3. In contrast, LSPCs in aggressive AML were characterized by a higher activation of stemness/proliferation-related pathways and develop independent of BM CD8+ T cells. Overall, our study indicates that CD8+ T cells support and expand LSPCs in favorable risk AML whereas intermediate and adverse risk AML possess the intrinsic molecular abnormalities to develop independently.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Radpour, Ramin; Riether, Carsten; Höpner, Sabine; Bruggmann, Rémy and Ochsenbein, Adrian

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0887-6924

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Rebeka Gerber

Date Deposited:

31 Oct 2019 14:00

Last Modified:

31 Dec 2019 11:05

Publisher DOI:

10.1038/s41375-019-0441-9

PubMed ID:

30877275

BORIS DOI:

10.7892/boris.134306

URI:

https://boris.unibe.ch/id/eprint/134306

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