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Proc Natl Acad Sci U S A ; 117(25): 14331-14341, 2020 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-32513686

RESUMEN

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.


Asunto(s)
Médula Ósea/metabolismo , Leucemia Mieloide Aguda/metabolismo , Linfocitos T/metabolismo , Microambiente Tumoral/fisiología , Médula Ósea/inmunología , Antígeno CTLA-4/metabolismo , Proliferación Celular , Citocinas/metabolismo , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Humanos , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/terapia , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos T/inmunología
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