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

Adam J. Lamble, Yoko Kosaka, Ted Laderas, Allie Maffit, Andy Kaempf, Lauren K. Brady, Weiwei Wang, Nicola Long, Jennifer N. Saultz, Motomi Mori, David Soong, Clare V. LeFave, Fei Huang, Homer Adams, Marc M. Loriaux, Marc M. Loriaux, Cristina E. Tognon, Pierrette Lo, Jeffrey W. Tyner, Jeffrey W. TynerGuang Fan, Shannon K. McWeeney, Brian J. Druker, Brian J. Druker, Brian J. Druker, Evan F. Lind, Evan F. Lind, Evan F. Lind

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)14331-14341
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number25
DOIs
StatePublished - Jun 23 2020

Keywords

  • AML
  • Checkpoint blockade
  • Immune microenvironment
  • Leukemia
  • T cell

ASJC Scopus subject areas

  • General

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