The Formation and Therapeutic Update of Tumor-Associated Macrophages in Cervical Cancer
Abstract
:1. Introduction
2. The Origins and Categories of Macrophages
2.1. Tissue-Resident Macrophages
2.2. Infiltrating Macrophages
3. The Molecules Involved in Forming TAMs
3.1. Tumor-Derived Molecules
3.1.1. Molecules Promoting the Differentiation of Monocytes to TAMs
3.1.2. Molecules Promoting the Activation of TAMs
3.1.3. The role of Oncoproteins on TAMs Formation in CC
3.2. T Cell-Derived Molecules
3.3. Seminal Plasma-Derived Molecules
3.4. Anaerobic Microenvironment
4. Biomarkers of TAMs
5. The Switch from M2 to M1-like Macrophages
6. Development of Therapy by Targeting TAMs
6.1. Macrophages and Its Prognostic Value in CC
6.2. Therapy Targeting the Differentiation of TAMs
6.3. Therapy Targeting the Improvement of TAMs Anti-Tumor Activity
7. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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Categories | Characteristics |
---|---|
Tissue-resident macrophages | |
Infiltrating macrophages |
|
Categories | Name of Molecules | Potential Mechanism |
---|---|---|
Molecules promoting the differentiation of monocytes to TAMs | PGE2 and IL-6 [28] | |
Karyopherin β1 | Regulating the expression of transcriptional factors NFκB and AP-1 [29] | |
CCL2 /MCP-1 | ||
IL-10 | Inhibit the classic activation of macrophages through the JAK1/Tyk2/STAT3 pathway [31] | |
PRL | ||
Molecules promoting the activation of TAMs | FUCA-1 | |
GM-CSF | Promoting TAMs to release pro-tumor factors [35] | |
MIF [36] | ||
IL-10 |
Source | Name of Molecules | Potential Mechanism |
---|---|---|
T cell | IL-17 | |
IL-4 | Promoting M2a subtype polarization by inducing a transcriptional factor KLF4 [73] | |
IL-10 | Promoting M2c subtype polarization [44] | |
IL-4 and IL-10 | Promoting M2a subtype polarization [74] | |
Seminal plasma | Increasing the expression of COX2, PGE2, IL-6 in CC cells [75,76,77] | |
Anaerobic microenvironment | Promoting M2 polarization by overexpressing Nrp-1 in CC cells [78] |
Component | Potential Mechanism | |
---|---|---|
Targeting the differentiation of TAMs | CD4+ Th1 cells | Promoting TAMs to secret costimulatory molecules and the expression of CCR7 [28] |
rIFN-γ | Promoting TAMs to produce a diffusible tumoricidal substance [107] |
Molecules | Potential Mechanism | |
---|---|---|
Targeting the differentiation of TAMs | Ind. | Inhibiting the expression of PG [108] |
tocilizumab | Blocking IL-6R [109] | |
rIFN-γ | Simulating the role of IFN-γ to induce M2 to M1-like macrophages [16] | |
SLP | Inducing T cells to inflow [110] | |
Improvement in anti-tumor activity of TAMs | SPG | Inducing the cytotoxic activity of macrophage [111] |
MCP-3 | Activating the phagocytic ability of macrophages [112] | |
Pre-TNF | Increasing phagocytosis [113] | |
bovine papilloma virus antibody | Inducing the cytotoxic activity of macrophage [114] | |
PMMA | Stimulating TAMs to produce TNF-α [115] | |
6FN | Inducing TAMs to release anti-tumor cytokines [116] |
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Wang, Q.; Steger, A.; Mahner, S.; Jeschke, U.; Heidegger, H. The Formation and Therapeutic Update of Tumor-Associated Macrophages in Cervical Cancer. Int. J. Mol. Sci. 2019, 20, 3310. https://doi.org/10.3390/ijms20133310
Wang Q, Steger A, Mahner S, Jeschke U, Heidegger H. The Formation and Therapeutic Update of Tumor-Associated Macrophages in Cervical Cancer. International Journal of Molecular Sciences. 2019; 20(13):3310. https://doi.org/10.3390/ijms20133310
Chicago/Turabian StyleWang, Qun, Alexander Steger, Sven Mahner, Udo Jeschke, and Helene Heidegger. 2019. "The Formation and Therapeutic Update of Tumor-Associated Macrophages in Cervical Cancer" International Journal of Molecular Sciences 20, no. 13: 3310. https://doi.org/10.3390/ijms20133310