Page 58 - Read Online

Gurska et al. Cancer Drug Resist 2023;6:674-87 Cancer
DOI: 10.20517/cdr.2023.39
Drug Resistance

Review Open Access

Unveiling T cell evasion mechanisms to immune
checkpoint inhibitors in acute myeloid leukemia

1
Lindsay Gurska , Kira Gritsman 1,2
1
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
2
Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Correspondence to: Dr. Kira Gritsman, Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park
Avenue, Chanin 410, Bronx, NY 10461, USA. E-mail: kira.gritsman@einsteinmed.edu
How to cite this article: Gurska L, Gritsman K. Unveiling T cell evasion mechanisms to immune checkpoint inhibitors in acute
myeloid leukemia. Cancer Drug Resist 2023;6:674-87. https://dx.doi.org/10.20517/cdr.2023.39

Received: 1 May 2023 First Decision: 31 May 2023 Revised: 1 Jul 2023 Accepted: 21 Sep 2023 Published: 26 Sep 2023
Academic Editor: Godefridus J. Peters Copy Editor: Pei-Yun Wang Production Editor: Pei-Yun Wang

Abstract
Acute myeloid leukemia (AML) is a heterogeneous and aggressive hematologic malignancy that is associated with
a high relapse rate and poor prognosis. Despite advances in immunotherapies in solid tumors and other
hematologic malignancies, AML has been particularly difficult to treat with immunotherapies, as their efficacy is
limited by the ability of leukemic cells to evade T cell recognition. In this review, we discuss the common
mechanisms of T cell evasion in AML: (1) increased expression of immune checkpoint molecules;
(2) downregulation of antigen presentation molecules; (3) induction of T cell exhaustion; and (4) creation of an
immunosuppressive environment through the increased frequency of regulatory T cells. We also review the clinical
investigation of immune checkpoint inhibitors (ICIs) in AML. We discuss the limitations of ICIs, particularly in the
context of T cell evasion mechanisms in AML, and we describe emerging strategies to overcome T cell evasion,
including combination therapies. Finally, we provide an outlook on the future directions of immunotherapy research
in AML, highlighting the need for a more comprehensive understanding of the complex interplay between AML
cells and the immune system.

Keywords: Acute myeloid leukemia, T cells, immune checkpoint, immune evasion

INTRODUCTION
Acute myeloid leukemia (AML) is a devastating blood cancer and is the most common form of acute

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

www.cdrjournal.com