Diet-Induced Obesity Impairs Outcomes and Induces Multi-Factorial Deficiencies in Effector T Cell Responses Following Anti-CTLA-4 Combinatorial Immunotherapy in Renal Tumor-Bearing Mice
Abstract
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Animals and Diets
2.2. Murine In Vivo Tumor Modeling
2.3. NanoString Immunogenetic Profiling
2.4. Flow Cytometry
2.5. Tumor-Specific Protein Quantification
2.6. Statistical Analysis
3. Results
3.1. Combinatorial Therapy Induces the Greatest Reduction in Tumor Growth and Expansion in CD44+CD8+ Tumor-Infiltrating Lymphocytes (TILs) in Young, Chow-Fed Mice
3.2. Therapy-Treated OB-RES Mice Have a Sustained Reduction in Tumor Growth over Time; Therapy-Treated DIO Mice Experience an Acute, Transient Response Followed by Tumor Outgrowth
3.3. Therapy-Treated OB-RES Mice Display an Immunogenetic Profile Characterized by Increased Expression of T Cell Related Genes and Biological Processes
3.4. Therapy-Treated OB-RES Mice Possess an Intratumoral Milieu Favoring T Cell Chemoattractants and Reductions in Pro-Inflammatory Mediators
3.5. Therapy-Treated OB-RES Mice Have an Enhanced CD44+CD4+ TIL Response
3.6. Therapy-Treated OB-RES Mice Have a Sustained CD44+CD8+ TIL Response over Time
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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Turbitt, W.J.; Boi, S.K.; Gibson, J.T.; Orlandella, R.M.; Norian, L.A. Diet-Induced Obesity Impairs Outcomes and Induces Multi-Factorial Deficiencies in Effector T Cell Responses Following Anti-CTLA-4 Combinatorial Immunotherapy in Renal Tumor-Bearing Mice. Cancers 2021, 13, 2295. https://doi.org/10.3390/cancers13102295
Turbitt WJ, Boi SK, Gibson JT, Orlandella RM, Norian LA. Diet-Induced Obesity Impairs Outcomes and Induces Multi-Factorial Deficiencies in Effector T Cell Responses Following Anti-CTLA-4 Combinatorial Immunotherapy in Renal Tumor-Bearing Mice. Cancers. 2021; 13(10):2295. https://doi.org/10.3390/cancers13102295
Chicago/Turabian StyleTurbitt, William J., Shannon K. Boi, Justin T. Gibson, Rachael M. Orlandella, and Lyse A. Norian. 2021. "Diet-Induced Obesity Impairs Outcomes and Induces Multi-Factorial Deficiencies in Effector T Cell Responses Following Anti-CTLA-4 Combinatorial Immunotherapy in Renal Tumor-Bearing Mice" Cancers 13, no. 10: 2295. https://doi.org/10.3390/cancers13102295
APA StyleTurbitt, W. J., Boi, S. K., Gibson, J. T., Orlandella, R. M., & Norian, L. A. (2021). Diet-Induced Obesity Impairs Outcomes and Induces Multi-Factorial Deficiencies in Effector T Cell Responses Following Anti-CTLA-4 Combinatorial Immunotherapy in Renal Tumor-Bearing Mice. Cancers, 13(10), 2295. https://doi.org/10.3390/cancers13102295