Thrombospondin-1 Silencing Improves Lymphocyte Infiltration in Tumors and Response to Anti-PD-1 in Triple-Negative Breast Cancer
Abstract
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. In Silico Analyses
2.2. Patients
2.3. Immunohistochemistry
2.4. Cell Lines and Transduction
2.5. Animal Model
2.6. Quantification of Lung Metastasis
- Luciferase forward primer: 5′TCTAAAACGGATTACCAGGGATTT;
- Luciferase reverse primer: 5′ACCGGGAGGTAGATGAGATGTG;
- Cyclophilin A forward primer: 5′GTCAACCCCACCGTGTTCTT;
- Cyclophilin A reverse primer: 5′CTGCTGTCTTTGGGACCTTGT.
2.7. Immunotherapy in Mice
2.8. Flow Cytometry
2.9. Statistical Analysis
3. Results
3.1. TSP1 Expression Is Associated with a Poor Prognosis in TNBC Patients and a Low CD8+ T Cell Infiltration in Tumors
3.2. TSP1 Inhibition in Murine Breast Cancer Cells Thwarts Metastasis in Immunocompetent but Not Immunodeficient Mice
3.3. Impacts of TSP1 Knockdown on Tumor Vascularization and T Cell Infiltration
3.4. TSP1 Knockdown Enhances Anti-PD-1 Therapy Efficacy in Mice
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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Marcheteau, E.; Farge, T.; Pérès, M.; Labrousse, G.; Tenet, J.; Delmas, S.; Chusseau, M.; Duprez-Paumier, R.; Franchet, C.; Dalenc, F.; et al. Thrombospondin-1 Silencing Improves Lymphocyte Infiltration in Tumors and Response to Anti-PD-1 in Triple-Negative Breast Cancer. Cancers 2021, 13, 4059. https://doi.org/10.3390/cancers13164059
Marcheteau E, Farge T, Pérès M, Labrousse G, Tenet J, Delmas S, Chusseau M, Duprez-Paumier R, Franchet C, Dalenc F, et al. Thrombospondin-1 Silencing Improves Lymphocyte Infiltration in Tumors and Response to Anti-PD-1 in Triple-Negative Breast Cancer. Cancers. 2021; 13(16):4059. https://doi.org/10.3390/cancers13164059
Chicago/Turabian StyleMarcheteau, Elie, Thomas Farge, Michaël Pérès, Guillaume Labrousse, Julie Tenet, Stéphanie Delmas, Maud Chusseau, Raphaëlle Duprez-Paumier, Camille Franchet, Florence Dalenc, and et al. 2021. "Thrombospondin-1 Silencing Improves Lymphocyte Infiltration in Tumors and Response to Anti-PD-1 in Triple-Negative Breast Cancer" Cancers 13, no. 16: 4059. https://doi.org/10.3390/cancers13164059
APA StyleMarcheteau, E., Farge, T., Pérès, M., Labrousse, G., Tenet, J., Delmas, S., Chusseau, M., Duprez-Paumier, R., Franchet, C., Dalenc, F., Imbert, C., Noujarède, J., Colacios, C., Prats, H., Cabon, F., & Ségui, B. (2021). Thrombospondin-1 Silencing Improves Lymphocyte Infiltration in Tumors and Response to Anti-PD-1 in Triple-Negative Breast Cancer. Cancers, 13(16), 4059. https://doi.org/10.3390/cancers13164059