Treg Cell Therapeutic Strategies for Breast Cancer: Holistic to Local Aspects
Abstract
:1. Introduction
2. Treg Classification and Characteristics
2.1. Treg Classification
2.2. Treg Characteristics
3. Identification of Tregs
3.1. Flow Cytometry
3.2. Transcriptomics
3.3. Proteomics
4. Treg Interactions in BC
4.1. Chemokine Recruitment of Tregs
4.2. Treg Immunosuppression of Tumors
4.3. BC Metabolism and Treg Effects
4.4. Tregs Enhance Tumor Progression, Metastasis and Drug Resistance
5. Immune-Targeted Therapy against Tregs
5.1. CTLA-4-Targeting Antibody
5.2. PD-1/PD-L1-Targeted Antibodies
5.3. Anti-GITR-Targeting Antibodies
5.4. Immunoassistant Molecules of Anti-Treg
5.5. Cytokine Inhibitors of Treg
5.5.1. Anti-CD25 Antibody
5.5.2. TGF-β and GARP
5.6. Inhibition of Treg Chemotaxis
5.6.1. CCR8 Inhibitors
5.6.2. CCR4-CCL17/CCL22 Antagonists
5.6.3. CCR5/CCL5
5.7. Interference with Treg Metabolism
5.7.1. Adenosine Inhibitors
5.7.2. Indoleamine 2,3-Dioxygenase (IDO) Inhibitors
5.8. Foxp3 Vaccine
5.9. Exosomes and Tregs
5.10. Nano-Engineered Targeting of Tregs
5.11. Tregs in Combination with Radiotherapy
6. Challenges
7. Future Directions
8. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Nanocarrier | Size (nm) | Supportive Measures | Treg Level | Other Marker Levels | Breast Cancer Model | Ref. |
---|---|---|---|---|---|---|
Lipid | 176.5 ± 62.23 nm | UA | Down | pSTAT5; IL-10; IL-6 ↓ | 4T1 mice | [267] |
PEG2k-Fmoc-NLG | 90 nm | PTX | Down | IFN-γ+ CD4+; CD8+ T; M1 Macrophages; G-MDSC ↑ M2 Macrophages ↓ | 4T1.2 mice | [259] |
DOX/IND@NPs | 104 ± 3.21 nm | IND+DOX | Down | CD8+ T ↑; VEGF; MMP9; CD31 ↓ | 4T1 mice | [259] |
PNT/DOX NPs | 232.0 ± 11.5 nm | DOX+R837 | Down | IL-6; IL-12; TNF-α; IFN-γ; DC ↑ | 4T1 mice | [267] |
L@S/L | 100 nm | LND+Sy | Down | M1 Macrophages; NK ↑ M2 Macrophages; Lactic acid ↓ | 4T1 mice | [267] |
PEG2k-Fmoc-IL36 | <450 nm | Anti-CTLA-4mAb | Down | IFN-γ+ CD4+T ↑ IFN-γ+ CD8+ T ↑ | 4T1.2 Lung metastasis mice | [259] |
ChLa NPs | 100 nm | CD73-specific siRNA+DC vaccine | Down | IFN-γ ↑ CD73; A2AR; IL-10; IL-17 ↓ | 4T1 mice | [259] |
PCL NPs | 100 nm | A2AR-specific siRNA | Down | IFN-γ ↑ IL-10; A2AR ↓ | 4T1 mice | [259] |
PD-1@PTX 2 NPs | 203.7 nm | PTX | Down | TNF-α; IFN-γ ↑; CD8+ T ↑ (3.2 times) | 4T1 mice | [259] |
DACss | 73.67 ± 1.80 nm | DMC+Anti-PD-1mAb+PDT | Down | ROS ↑ CD80+ CD86+ DC ↑ | 4T1 mice | [270] |
CA@α-LA | 175.0 ± 8.4 nm | Anti-Nrp-1 mAb | Down | Caspase-3; Bcl-2 ↑ VEGF ↓ | 4T1 mice | [259] |
Polymer-coated IONPs | 30.7 ± 1.8 nm | Anti-CTLA-4 mAb+PTT | Down | CD8+ T ↑ | 4T1 mice | [270] |
CuS | 84 ± 3.0 nm | EPDA +PTT | Down | ROS ↑ Ki-67; IDO-1; c-KIT; EPHA2; PDGFRβ ↓ | 4T1 mice | [259] |
PCL-Hyd-PEG | 150 nm | Tumor endogenous antigens (HCP)+ adjuvants CpG ODN+ Anti-CD80 mAb | Down | IFN-γ; CD4+ T; CD8+ T ↑ | 4T1 rat | [259] |
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Zhang, H.; Felthaus, O.; Eigenberger, A.; Klein, S.; Prantl, L. Treg Cell Therapeutic Strategies for Breast Cancer: Holistic to Local Aspects. Cells 2024, 13, 1526. https://doi.org/10.3390/cells13181526
Zhang H, Felthaus O, Eigenberger A, Klein S, Prantl L. Treg Cell Therapeutic Strategies for Breast Cancer: Holistic to Local Aspects. Cells. 2024; 13(18):1526. https://doi.org/10.3390/cells13181526
Chicago/Turabian StyleZhang, Hanwen, Oliver Felthaus, Andreas Eigenberger, Silvan Klein, and Lukas Prantl. 2024. "Treg Cell Therapeutic Strategies for Breast Cancer: Holistic to Local Aspects" Cells 13, no. 18: 1526. https://doi.org/10.3390/cells13181526