Tissue- and Temporal-Dependent Dynamics of Myeloablation in Response to Gemcitabine Chemotherapy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Line and Animal Maintenance
2.2. Gemcitabine Therapy
2.3. Flow Cytometry
2.4. BFA Injections
2.5. RNA Extraction, QC, and Library Preparations
2.6. RNA-Seq Analysis
- Quality control
- 2.
- Mapping and quantitation
- 3.
- Differential gene expression analysis (DGE):
- 4.
- Pathway Analysis
In Vivo Anti-IFN-γ Delivery
2.7. Statistical Analysis
3. Results
3.1. Gemcitabine Was Not Acutely Myeloablative in the Tumor Microenvironment
3.2. GEM Significantly Lowered the Abundance of TILs and Dendritic Cells in the TNBC TME
3.3. GEM Treatment Acutely Upregulated Genes Associated with Immune Pathways in TNBC Tumors
3.4. Production of IFN-γ, Which Is Predominately Secreted by Granulocytic Cells in the TME, Was Altered by GEM
3.5. GEM-Mediated Tumor Growth Control Was Not Dependent on IFN-γ
3.6. GEM Treatment Altered Arginase 1 Expression by Myeloid Cells in TNBC Tumors
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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Kitelinger, L.E.; Thim, E.A.; Zipkowitz, S.Y.; Price, R.J.; Bullock, T.N.J. Tissue- and Temporal-Dependent Dynamics of Myeloablation in Response to Gemcitabine Chemotherapy. Cells 2024, 13, 1317. https://doi.org/10.3390/cells13161317
Kitelinger LE, Thim EA, Zipkowitz SY, Price RJ, Bullock TNJ. Tissue- and Temporal-Dependent Dynamics of Myeloablation in Response to Gemcitabine Chemotherapy. Cells. 2024; 13(16):1317. https://doi.org/10.3390/cells13161317
Chicago/Turabian StyleKitelinger, Lydia E., Eric A. Thim, Sarah Y. Zipkowitz, Richard J. Price, and Timothy N. J. Bullock. 2024. "Tissue- and Temporal-Dependent Dynamics of Myeloablation in Response to Gemcitabine Chemotherapy" Cells 13, no. 16: 1317. https://doi.org/10.3390/cells13161317