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Review
. 2022 Feb 22:13:811144.
doi: 10.3389/fimmu.2022.811144. eCollection 2022.

Tumor Microenvironment in Acute Myeloid Leukemia: Adjusting Niches

Thomas Menter  1 , Alexandar Tzankov  1
Affiliations
Review

Tumor Microenvironment in Acute Myeloid Leukemia: Adjusting Niches

Thomas Menter et al. Front Immunol. .

Abstract

Acute myeloid leukemias (AML) comprise a wide array of different entities, which have in common a rapid expansion of myeloid blast cells leading to displacement of normal hematopoietic cells and also disruption of the microenvironment in the bone marrow niches. Based on an insight into the complex cellular interactions in the bone marrow niches in non-neoplastic conditions in general, this review delineates the complex relationship between leukemic cells and reactive cells of the tumor microenvironment (TME) in AML. A special focus is directed on niche cells and various T-cell subsets as these also provide a potential therapeutic rationale considering e.g. immunomodulation. The TME of AML on the one hand plays a vital role for sustaining and promoting leukemogenesis but - on the other hand - it also has adverse effects on abnormal blasts developing into overt leukemia hindering their proliferation and potentially removing such cells. Thus, leukemic cells need to and develop strategies in order to manipulate the TME. Interference with those strategies might be of particular therapeutic potential since mechanisms of resistance related to tumor cell plasticity do not apply to it.

Keywords: AML; T-cells; TME; bone marrow niches; bone marrow stromal cells.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Distribution of nestin+ cells of the perivascular niches in AML. (A) Nestin expression in MSC-equivalents in normal bone marrow (immunohistochemistry, 400x); (B) Increased presence of nestin-positive MSC-equivalents in a case of AML suggesting importance of the former cells for AML survival (immunohistochemistry, 400x).
Figure 2
Figure 2
Expression of hyaluronic acid binding proteins in AML. (A) Diffuse expression of RHAMM in AML cells (immunohistochemistry, 400x); (B) Diffuse expression of CD44v6 in AML cells (immunohistochemistry, 400x).
Figure 3
Figure 3
Distribution of PD-L1+ mononuclear tumor-infiltrating cells in AML. Case of relapsing AML showing high expression of PD-L1 (B) in contrast to very scarce expression of PD-L1 in the adjacent non-neoplastic bone marrow (A; immunohistochemistry, 200x).
Figure 4
Figure 4
Distribution of regulatory T-cells and TH1-cells in AML. Presence of regulatory T-cells expressing FOXP3 (A) and Tbet (B) in bone marrow involved by AML (immunohistochemistry, 400x).
Figure 5
Figure 5
Expression of members of the CXCL12-CXCR4 axis in AML. (A) Expression of CXCL12 in perivascular MSC-equivalents in AML (immunohistochemistry, 400x); (B) Diffuse expression of the receptor of CXCL12, CXCR4, on AML blasts (immunohistochemistry, 400x).
Figure 6
Figure 6
Schematic summarizing some interactions of AML with the TME. Stimulatory signaling is delineated in red, inhibitory – in green; tumor-promoting cells are blueish, tumor-suppressing cells – greenish, while niche-cells and nutrient-supplying cells are yellowish. The scheme does not claim to be complete and mainly reflects aspects that have been addressed in this review. For abbreviations, we kindly refer to the manuscript body.
See this image and copyright information in PMC

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