Immune Evasion in Cancer Metastasis: An Unappreciated Role of Monocytes
Simple Summary
Abstract
1. Introduction
2. Formation and Characteristics of Monocytes
3. Pro-Metastatic Role of Monocytes in the Bloodstream
4. Monocytes and Circulating Tumor Cells: Cooperation Towards Tumor Hybrid Cells
5. Primary Tumor: The Contribution of Monocytes in Cancer Cell Intravasation
6. Role of Monocytes in the Pre-Metastatic Niche Formation and Metastasis
6.1. Pre-Metastatic Niche
6.2. Metastasis
6.3. Contribution of Non-Classical Monocyte Populations
7. Targeting Monocytes to Suppress Metastasis
7.1. Blockade of Monocyte Recruiting
7.2. Monocyte Reprogramming
7.3. Monocytes as Therapeutical Carriers
7.4. Targeting Mo-MDSCs
8. Concluding Remarks
Author Contributions
Funding
Conflicts of Interest
Abbreviations
CyTOF | cytometry by the time of flight |
CAFs | cancer-associated fibroblasts |
CAR | chimeric antigen receptor |
CTCs | circulating tumor cells |
EMT | epithelial-mesenchymal transition |
IFN-γ | interferon gamma |
HER2 | human epidermal growth factor receptor 2 |
IL | interleukin |
MCP-1 | monocyte chemotactic protein-1 |
MCP-3 | monocyte chemotactic protein-3 |
Mo-MDSCs | monocytic myeloid-derived suppressor cells |
MMP | matrix metalloproteinase |
M-SMNs | self-assembled into nanoparticles monocytes |
MMTV-PyMT | middle T-antigen breast cancer metastasis model |
NK | natural killer cells |
PD1 | programmed cell death 1 |
PD-L1 | programmed cell death 1 ligand 1 |
PDAC | pancreatic ductal adenocarcinoma |
PMN | pre-metastatic niche |
SDF-1α | stromal-derived factor 1 |
TAMs | tumor-associated macrophages |
TGF-β | transforming growth factor beta |
THCs | tumor hybrid cells |
TNF-α | tumor necrosis factor alpha |
VCAM-1 | vascular cell adhesion molecule-1 |
VEGF | vascular endothelial growth factor |
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Cancer Type | Monocyte Clusters | Markers | Refs |
---|---|---|---|
Lung cancer (N = 7) |
| 1. CD14, FCN1, OLR1 2. CDKN1C, LILRB2, ITGAL 3. S100A8, S100A9, CSF3R, PROK2, VCAN | [55] |
Colorectal cancer (N = 5) |
| Not specified | [54] |
Breast cancer Lung cancer (N = 10) |
|
| [56] |
Ovarian cancer (N = 3) |
|
| [57] |
Melanoma (N = 66) | 1.Subgroup 0 2. Subgroup 1 3. Subgroup 2 4. Subgroup 3 5. Subgroup 4 6. Subgroup 5 7. Subgroup 6 8. Subgroup 7 9. Subgroup 8 10. Subgroup 9 11. Subgroup 10 12. Subgroup 11 13. Subgroup 12 14. Subgroup 13 15. Subgroup 14 16. Subgroup 15 17/18. Subgroup 16/17 | 1. RPS26, RPL7, RPS3A, RPL21, EEF1A1 2. S100A12, S100A8, S100A9 3. IFI2, IFIT3, ILRN1, CXCL10 4. CXCL9, HLA-DRB5, HLA-DQA1 5. RPS26, RPL7, RPS3A, RPL21 6. CLEC5A, TGFB1, FN1, YWHAH, FBP1 7. RSAD2, CSTB, HSPH1, DNAJB1 8. FCGR3A, CDKN1C, NAP1L1, SPN 9. FOS, ZFP36, BTG1, GPR183, IER3 10. CD163, IFI6, RNASE1, C1QC, C1QA 11. AREG, EREG, THBS1, THBD, TIMP1 12. PLIN2, IL8, HSP90AA1 13. TRAC, TRBC2, GZMA, CCL5 14. NFKBIA, EGR1, NFKBIZ, IL1B 15. FABP5, APOC1, SPP1, HMOX, APOE 16. CXCL3, CXCL2, CXCL8 17/18. C1QB, IFI27, NUPR1 | [58] |
Location | Cancer Secreted Factors | Monocyte Cell Response | Cancer Types/Models |
---|---|---|---|
Bloodstream | CCL2, CCL5, CCL7, and CCL12 | Recruitment of monocytes via CCR2 | Lung, pancreatic cancer |
Tumor microparticles | Recruitment of monocytes via CCR2 Pro-tumor macrophage differentiation | Colorectal cancer | |
TNF-α | Formation of hetero-aggregates between tumor cells and monocytes via upregulation of ICAM-1 | Prostate and breast cancers | |
CD36 | THC formation with anti-inflammatory polarized monocytes | Colorectal, lung, and prostate cancers | |
Primary tumor | TGF-β, CXCL12 | Recruitment of monocytes via CCR2, CXCR4 | Breast cancer |
IL-1β | Monocytes promote tumor cell adhesion to endothelial via upregulation of E-selectin | Colorectal cancer | |
PMN | CCL2 | Recruitment of monocytes and Mo-MDSCs and their differentiation towards pro-tumorigenic macrophages | Colorectal, breast cancer, melanoma |
TNF-α, TGF-β, VEGF-α | Monocyte extravasation into the PMN via S100A8/A9 | Lung metastasis of LLC, B16 mice tumors | |
CCL12 | Recruitment of Mo-MDSCs and promoting them to secrete: 1. IL-1β, IL-6, IL-10, TGF-b, and VEGF involved in EMT; 2. arginase-1 and ROS which creates a suppressive immune microenvironment; 3. CCL7 activating dormant micro-metastatic cells | Metastatic melanoma, colorectal cancer | |
Metastatic site | VCAM-1 | Monocytes upregulate migratory chemokines (CXCL3, IL8, ILB, CXCL2, CXCL5, CCL20, CCL3), tumor cell proliferation factors (AREG, EREG, SPP1) throught α4-integrin receptor binding | Breast cancer metastatic cells, pancreatic cancer, melanoma brain and leptomeningeal metastases |
Strategy | Approach | Mechanism | Effect | Current Stage | Refs |
---|---|---|---|---|---|
Blockade of monocyte recruitment | Monoclonal antibodies or antagonists | Target CCR2 or CCL2 | Metastasis inhibition in mice models of hepatocellular carcinoma | Pre-clinical | [129,130] |
CCR2+ monocytes decreasing | Phase II clinical trials | [131] | |||
Monocyte reprogramming strategies | Tumor-derived extracellular vesicles (TEVs) | Releasing of IL-1β and TNF-α cytokines | Induction the immediate-early response | Cell cultures | [132] |
MicroRNA |
CCL2 inhibition | Lung metastasis inhibition in mouse model of breast cancer | Pre-clinical | [133,134,135] | |
Exosomes |
| Metastasis inhibion in mice models of melanoma | Pre-clinical | [127] | |
Small-molecule activators of NOD2 | Metastasis inhibion in mice models of melanoma, lung, breast and colon cancers | Pre-clinical | [136] | ||
Monocytes as therapeutical carriers | M-SMNs | Tumor cytotoxicity | Lung metastasis inhibition in mouse model of breast cancer | Pre-clinical | [137] |
CAR-M |
Cytokines and chemokines secretion | Lung metastasis inhibition in mouse model of ovarian cancer | Pre-clinical; Clinical studies Phase 1 | [138,139] | |
Targeting Mo-MDSC | Monoclonal antibodies, peptides, small molecular inhibitors |
| Reducing Mo-MDSCs | Pre-clinical; Phase II clinical trials | [140,141,142] |
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Patysheva, M.R.; Fedorenko, A.A.; Khozyainova, A.A.; Denisov, E.V.; Gerashchenko, T.S. Immune Evasion in Cancer Metastasis: An Unappreciated Role of Monocytes. Cancers 2025, 17, 1638. https://doi.org/10.3390/cancers17101638
Patysheva MR, Fedorenko AA, Khozyainova AA, Denisov EV, Gerashchenko TS. Immune Evasion in Cancer Metastasis: An Unappreciated Role of Monocytes. Cancers. 2025; 17(10):1638. https://doi.org/10.3390/cancers17101638
Chicago/Turabian StylePatysheva, Marina R., Anastasya A. Fedorenko, Anna A. Khozyainova, Evgeny V. Denisov, and Tatiana S. Gerashchenko. 2025. "Immune Evasion in Cancer Metastasis: An Unappreciated Role of Monocytes" Cancers 17, no. 10: 1638. https://doi.org/10.3390/cancers17101638
APA StylePatysheva, M. R., Fedorenko, A. A., Khozyainova, A. A., Denisov, E. V., & Gerashchenko, T. S. (2025). Immune Evasion in Cancer Metastasis: An Unappreciated Role of Monocytes. Cancers, 17(10), 1638. https://doi.org/10.3390/cancers17101638