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Nanoparticle-Based Drug Delivery Systems Targeting Tumor Microenvironment for Cancer Immunotherapy Resistance:
Peijie Wu1,2, Jun Han1, Yanju Gong1
1School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China.
Abstract:
Cancer immunotherapy has shown impressive anti-tumor activity in patients with advanced and early-stage malignant tumors, thus improving long-term survival. However, current cancer immunotherapy is limited by barriers such as low tumor specificity, poor response rate, and systemic toxicities, which result in the development of primary, adaptive, or acquired resistance. Immunotherapy resistance has complex mechanisms that depend on the interaction between tumor cells and the tumor microenvironment (TME). Therefore, targeting TME has recently received attention as a feasibility strategy for re-sensitizing resistant neoplastic niches to existing cancer immunotherapy. With the development of nanotechnology, nanoplatforms possess outstanding features, including high loading capacity, tunable porosity, and specific targeting to the desired locus. Therefore, nanoplatforms can significantly improve the effectiveness of immunotherapy while reducing its toxic and side effects on non-target cells that receive intense attention in cancer immunotherapy. This review explores the mechanisms of tumor microenvironment reprogramming in immunotherapy resistance, including TAMs, CAFs, vasculature, and hypoxia. We also examined whether the application of nano-drugs combined with current regimens is improving immunotherapy clinical outcomes in solid tumors.
Insights
Nanotechnology offers a promising strategy to overcome cancer immunotherapy resistance by targeting the tumor microenvironment (TME). Nanoplatforms can enhance treatment efficacy and reduce side effects in solid tumors.
Area of Science:
- Oncology
- Nanotechnology
- Immunotherapy
Background:
- Cancer immunotherapy demonstrates significant anti-tumor activity but faces limitations like resistance and toxicity.
- Resistance mechanisms involve complex interactions between tumor cells and the tumor microenvironment (TME).
- Targeting the TME is a viable strategy to re-sensitize tumors to immunotherapy.
Purpose of the Study:
- To explore TME reprogramming mechanisms contributing to immunotherapy resistance.
- To evaluate the potential of nanoplatforms in overcoming immunotherapy resistance.
- To examine the clinical impact of nano-drugs combined with immunotherapy for solid tumors.
Main Methods:
- Review of mechanisms of tumor microenvironment reprogramming (TAMs, CAFs, vasculature, hypoxia).
- Analysis of nanoplatform characteristics (loading capacity, porosity, targeting).
- Examination of combined nano-drug and immunotherapy regimens in solid tumors.
Main Results:
- Nanoplatforms show potential for enhanced immunotherapy effectiveness and reduced toxicity.
- Targeting TME components like TAMs and CAFs is crucial for overcoming resistance.
- Combined nano-drug strategies may improve clinical outcomes in solid tumors.
Conclusions:
- Nanotechnology-based approaches hold significant promise for improving cancer immunotherapy.
- Understanding TME dynamics is key to developing more effective cancer treatments.
- Further investigation into nano-drug combinations is warranted for solid tumor treatment.
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