Vascular-Associated Mononuclear Phagocytes: First-Line Soldiers Ambushing Metastasis
Han-Ying Huang1, Xin-Nan Zheng1, Lin Tian1
1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
Abstract:
Mononuclear phagocytes (MPs), which consist of dendritic cells, monocytes, and macrophages, are distributed throughout the body and actively eliminate invading microorganisms and abnormal cells. Depending on the local microenvironment, MPs manifest considerably various lifespans and phenotypes to maintain tissue homeostasis. Vascular-associated mononuclear phagocytes (VaMPs) are the special subsets of MPs that are localized either within the lumen side or on the apical surface of vessels, acting as the critical sentinels to recognize and defend against disseminated tumor cells. In this review, we introduce three major types of VaMPs, patrolling monocytes, Kupffer cells, and perivascular macrophages, and discuss their emerging roles in immunosurveillance during incipient metastasis. We also explore the roles of lineage-determining transcription factors and cell surface receptors that endow VaMPs with potent anti-tumor activity. Finally, we highlight the molecular and cellular mechanisms that drive the phenotypic plasticity of VaMPs and summarize combinatory strategies for targeting VaMPs in overt metastasis.
Insights
Vascular-associated mononuclear phagocytes (VaMPs) patrol blood vessels, identifying and fighting early-stage cancer spread. Understanding their plasticity and targeting them offers new metastasis treatment strategies.
Area of Science:
- Immunology
- Cell Biology
- Oncology
Background:
- Mononuclear phagocytes (MPs) maintain tissue homeostasis by eliminating abnormal cells.
- Vascular-associated mononuclear phagocytes (VaMPs) are crucial sentinels against disseminated tumor cells.
- VaMPs exhibit diverse lifespans and phenotypes influenced by their microenvironment.
Purpose of the Study:
- To review the roles of patrolling monocytes, Kupffer cells, and perivascular macrophages in immunosurveillance during incipient metastasis.
- To explore the molecular mechanisms, including transcription factors and cell surface receptors, underlying VaMP anti-tumor activity.
- To summarize strategies for targeting VaMPs in overt metastasis.
Main Methods:
- Literature review of existing research on mononuclear phagocytes and metastasis.
- Analysis of molecular and cellular mechanisms driving VaMP phenotypic plasticity.
- Synthesis of current knowledge on VaMP roles in immunosurveillance.
Main Results:
- Identified three key VaMP types: patrolling monocytes, Kupffer cells, and perivascular macrophages.
- Highlighted the importance of lineage-determining transcription factors and cell surface receptors in VaMP anti-tumor functions.
- Discussed the phenotypic plasticity of VaMPs in response to the microenvironment.
Conclusions:
- VaMPs play a critical role in immunosurveillance against early-stage cancer metastasis.
- Targeting VaMPs presents a promising therapeutic strategy for managing overt metastasis.
- Further research into VaMP plasticity can optimize anti-cancer treatments.
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