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Antitumor Research Based on Drug Delivery Carriers: Reversing the Polarization of Tumor-Associated Macrophages
Xinyu Cao1, Shen Wan1, Bingyu Wu1
1Department of Pharmaceutics, School of Pharmacy, Nantong University, Nantong 226001, China.
Abstract:
The development of malignant tumors is a complex process that involves the tumor microenvironment (TME). An immunosuppressive TME presents significant challenges to current cancer therapies, serving as a key mechanism through which tumor cells evade immune detection and play a crucial role in tumor progression and metastasis. This impedes the optimal effectiveness of immunotherapeutic approaches, including cytokines, immune checkpoint inhibitors, and cancer vaccines. Tumor-associated macrophages (TAMs), a major component of tumor-infiltrating immune cells, exhibit dual functionalities: M1-like TAMs suppress tumorigenesis, while M2-like TAMs promote tumor growth and metastasis. Consequently, the development of various nanocarriers aimed at polarizing M2-like TAMs to M1-like phenotypes through distinct mechanisms has emerged as a promising therapeutic strategy to inhibit tumor immune escape and enhance antitumor responses. This Review covers the origin and types of TAMs, common pathways regulating macrophage polarization, the role of TAMs in tumor progression, and therapeutic strategies targeting TAMs, aiming to provide a comprehensive understanding and guidance for future research and clinical applications.
Insights
The tumor microenvironment (TME) often suppresses immune responses, hindering cancer therapies. Targeting tumor-associated macrophages (TAMs) to shift their function offers a promising strategy to enhance antitumor immunity and combat cancer progression.
Area of Science:
- Oncology
- Immunology
- Nanotechnology
Background:
- The tumor microenvironment (TME) is critical in cancer development and immune evasion.
- An immunosuppressive TME impedes effective cancer immunotherapies like checkpoint inhibitors and vaccines.
- Tumor-associated macrophages (TAMs) are key immune cells within the TME, with M2-like TAMs promoting tumor growth.
Purpose of the Study:
- To review the origin, types, and polarization pathways of TAMs.
- To elucidate the role of TAMs in tumor progression and metastasis.
- To explore nanocarrier-based therapeutic strategies for TAM polarization to enhance antitumor responses.
Main Methods:
- Review of current literature on TAMs and their role in the TME.
- Analysis of mechanisms regulating macrophage polarization (M1 vs. M2).
- Examination of nanocarrier designs and their application in modulating TAM phenotypes.
Main Results:
- TAMs exhibit dual roles, with M2-like TAMs contributing to immunosuppression and tumor advancement.
- Nanocarriers offer a platform to reprogram M2-like TAMs towards an anti-tumorigenic M1-like phenotype.
- Targeting TAM polarization is a viable strategy to overcome immune escape and boost therapeutic efficacy.
Conclusions:
- Understanding TAM biology is crucial for developing effective cancer treatments.
- Nanotechnology-based approaches show potential for reprogramming TAMs to enhance anti-tumor immunity.
- Targeting TAMs represents a promising avenue for future cancer therapy development and clinical application.
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