Reversible suppression of T cell function in the bone marrow microenvironment of acute myeloid leukemia

Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with approximately four new cases per 100,000 persons per year. Standard treatment for AML consists of induction chemotherapy with remission achieved in 50 to 75% of cases. Unfortunately, most patients will relapse and die fro...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2020-06, Vol.117 (25), p.14331-14341
Main Authors: Lamble, Adam J., Kosaka, Yoko, Laderas, Ted, Maffit, Allie, Kaempf, Andy, Brady, Lauren K., Wang, Weiwei, Long, Nicola, Saultz, Jennifer N., Mori, Motomi, Soong, David, LeFave, Clare V., Huang, Fei, Adams, Homer, Loriaux, Marc M., Tognon, Cristina E., Lo, Pierrette, Tyner, Jeffrey W., Fan, Guang, McWeeney, Shannon K., Druker, Brian J., Lind, Evan F.
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
Biological Sciences
Bone marrow
Cell proliferation
Chemotherapy
CTLA-4 protein
Immune checkpoint
Leukemia
Lymphocytes
Lymphocytes T
Metastases
Myeloid leukemia
PD-1 protein
Remission
Survival
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Summary:Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with approximately four new cases per 100,000 persons per year. Standard treatment for AML consists of induction chemotherapy with remission achieved in 50 to 75% of cases. Unfortunately, most patients will relapse and die from their disease, as 5-y survival is roughly 29%. Therefore, other treatment options are urgently needed. In recent years, immune-based therapies have led to unprecedented rates of survival among patients with some advanced cancers. Suppression of T cell function in the tumor microenvironment is commonly observed and may play a role in AML. We found that there is a significant association between T cell infiltration in the bone marrow microenvironment of newly diagnosed patients with AML and increased overall survival. Functional studies aimed at establishing the degree of T cell suppression in patients with AML revealed impaired T cell function in many patients. In most cases, T cell proliferation could be restored by blocking the immune checkpoint molecules PD-1, CTLA-4, or TIM3. Our data demonstrate that AML establishes an immune suppressive environment in the bone marrow, in part through T cell checkpoint function.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1916206117