The Combination of Anti-CD47 Antibody with CTLA4 Blockade Enhances Anti-Tumor Immunity in Non-Small Cell Lung Cancer via Normalization of Tumor Vasculature and Reprogramming of the Immune Microenvironment
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Lines and Culture Conditions
2.2. Tumor Inoculation, Treatment, and Measurement
2.3. Fluorescence-Activated Cell Sorting (FACS)
2.4. Immunohistochemistry (IHC) and Immunofluorescence (IF)
2.5. Western Blot Analysis
2.6. Routine Blood Test in Mice
2.7. Statistical Analysis
3. Results
3.1. Dual CD47 and CTLA4 Blockade Impedes Tumor Growth and Improves Survival in NSCLC-Bearing Mice
3.2. Alteration of Immune Cell Reprogramming in TME and Potentiation of Immunotherapy Response in NSCLC-Bearing Mice by a Combination of Anti-CD47 Ab and Anti-CTLA4 Ab
3.3. Upregulation of CTLA4 Level in NSCLC Cells by Anti-CD47 Ab via Regulation of Foxp1
3.4. Anti-CD47 Ab Promotes Vascular Normalization of Tumors
3.5. Promotion of Tumor Vascular Normalization by Anti-CD47 Ab via Enhancement of CD4+ T Cell Tumor Infiltration
3.6. Alleviation of Anemia in NSCLC-Bearing Mice by Combined Targeting of CD47 and CTLA4
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Zhuang, Z.; Zhou, J.; Qiu, M.; Li, J.; Lin, Z.; Yi, H.; Liu, X.; Huang, C.; Tang, B.; Liu, B.; et al. The Combination of Anti-CD47 Antibody with CTLA4 Blockade Enhances Anti-Tumor Immunity in Non-Small Cell Lung Cancer via Normalization of Tumor Vasculature and Reprogramming of the Immune Microenvironment. Cancers 2024, 16, 832. https://doi.org/10.3390/cancers16040832
Zhuang Z, Zhou J, Qiu M, Li J, Lin Z, Yi H, Liu X, Huang C, Tang B, Liu B, et al. The Combination of Anti-CD47 Antibody with CTLA4 Blockade Enhances Anti-Tumor Immunity in Non-Small Cell Lung Cancer via Normalization of Tumor Vasculature and Reprogramming of the Immune Microenvironment. Cancers. 2024; 16(4):832. https://doi.org/10.3390/cancers16040832
Chicago/Turabian StyleZhuang, Zhan, Jinglin Zhou, Minglian Qiu, Jiamian Li, Zhuangheng Lin, Huihan Yi, Xuerong Liu, Changyu Huang, Binghua Tang, Bo Liu, and et al. 2024. "The Combination of Anti-CD47 Antibody with CTLA4 Blockade Enhances Anti-Tumor Immunity in Non-Small Cell Lung Cancer via Normalization of Tumor Vasculature and Reprogramming of the Immune Microenvironment" Cancers 16, no. 4: 832. https://doi.org/10.3390/cancers16040832