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Review
. 2022 Jan 28;23(3):1496.
doi: 10.3390/ijms23031496.

Repolarization of Unbalanced Macrophages: Unmet Medical Need in Chronic Inflammation and Cancer

Yannick Degboé  1   2 , Rémy Poupot  1 , Mary Poupot  3
Affiliations
Review

Repolarization of Unbalanced Macrophages: Unmet Medical Need in Chronic Inflammation and Cancer

Yannick Degboé et al. Int J Mol Sci. .

Abstract

Monocytes and their tissue counterpart macrophages (MP) constitute the front line of the immune system. Indeed, they are able to rapidly and efficiently detect both external and internal danger signals, thereby activating the immune system to eradicate the disturbing biological, chemical, or physical agents. They are also in charge of the control of the immune response and account for the repair of the damaged tissues, eventually restoring tissue homeostasis. The balance between these dual activities must be thoroughly controlled in space and time. Any sustained unbalanced response of MP leads to pathological disorders, such as chronic inflammation, or favors cancer development and progression. In this review, we take advantage of our expertise in chronic inflammation, especially in rheumatoid arthritis, and in cancer, to highlight the pivotal role of MP in the physiopathology of these disorders and to emphasize the repolarization of unbalanced MP as a promising therapeutic strategy to control these diseases.

Keywords: cancer; dendrimer; macrophages; monocyte; osteoclast; polarization; rheumatoid arthritis; tumor-associated macrophages.

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Conflict of interest statement

Rémy Poupot is co-founder and shareholder of IMD-Pharma.

Figures

Figure 1
Figure 1
Cytokine receptors of MP. BMP: bone morphogenic protein; CD: cluster differentiation; GM-CSF: granulocyte macrophage-colony stimulating factor; IL: interleukin, IL1-ra: interleukin-1 receptor antagonist; JAK: Janus kinases; IFN: interferon; IRAK: interleukin-1 receptor-associated kinase; MAPK: mitogen-activated protein kinases; MCP1: monocyte chemoattractant protein 1; MIP1: macrophage inflammatory protein 1; NGF: nerve growth factor; OSM: oncostatin M; STAT: signal transducer and activator of transcription; TNF: tumor necrosis factor.
Figure 2
Figure 2
Heterogeneity of the ontogeny of resident MP from adult tissues in mouse in the steady state. Taken from [14], copyright 2016 Elsevier Inc.
Figure 3
Figure 3
Description of activated MP. Functional classification of both mouse MP differentiated with M-CSF and monocyte-derived human MP. Taken from [32], copyright 2014 Elsevier Inc.
Figure 4
Figure 4
(A) Schematic synthesis of a generation 2 (2 series of branches) dendrimer using a tetravalent core (i.e., 4 branches in the first series) and trivalent points of divergence (i.e., 12 branches in the second series, and 36 surface groups). r1 and r2 are the reactions which are iterated to obtain the final dendrimer. (B) Structure of the dendrimer ABP. The cyclotriphosphazene core (N3P3) and the PPH branches (including the point of divergence) are in blue. The twelve tyramine-based (in blue) ABP surface groups are in red.
Figure 5
Figure 5
(A) Tumor development according to the M1 or M2 TAM phenotype in the TME: the M1 phenotype is induced by inflammatory molecules (yellow) and M2 phenotype by anti-inflammatory molecules (red). M1 TAM promote the killing of cancer cells and M2 TAM produce factors promoting tumor development. (B) Reprogramming of M2 TAM with: (i) monoclonal antibodies (mAb) or peptides targeting specific membranes receptors; (ii) small molecules targeting specific membrane proteins or penetrating into TAM; (iii) nanoparticles; (iv) other systems.
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