Low-Salt Diet Reduces Anti-CTLA4 Mediated Systemic Immune-Related Adverse Events while Retaining Therapeutic Efficacy against Breast Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Murine Breast Tumor Model
2.2. CD4+T Cell Isolation
2.3. Real Time Quantitative Polymerase Chain Reaction (RT-qPCR)
2.4. Western Blot
2.5. Luminex
2.6. Histochemical Staining
2.7. Sodium Magnetic Resonance Imaging
2.8. Electrolyte and Tissue Osmolarity Measurements
2.9. Enzyme Linked Immunosorbent Assay (ELISA)
2.10. Caspase 1 Activity Assay
2.11. Statistical Analysis
3. Results
3.1. Tumor and Plasma Electrolyte Changes following Salt Modified Diet
3.2. Anti-CTLA4 mAb Treatment in Low-Salt-Diet Cohort Enhanced the Survival
3.3. Low-Salt Diet Reduced Anti-CTLA4-Mediated Inflammatory Lung Infiltration
3.4. Low-Salt Diet Reduced Peripheral Inflammatory Cytokine Response and Alveolar Infiltration with Inflammatory CD4+T Cells following Anti-CTLA4 Therapy
3.5. Low-Salt Diet Downregulates NLRP3-Mediated Inflammasome Complex Leading to Diminished irAE
3.6. Osmosensitive Transcription Factor, NFAT5, Is a Critical Upstream Regulator in Anti-CTLA4 Induced irAE following High-Salt Diet
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Regular Diet | High Salt | Low Salt | |
---|---|---|---|
Effector Cytokines | |||
IL-1β | 427 ± 111 | 1453 ± 256 * | 203 ± 89 *,$ |
TNF-α | 511 ± 93 | 1818 ± 279 * | 367 ± 83 *,$ |
IFN-γ | 342 ± 77 | 1507 ± 301 * | 312 ± 84 * |
IL-17A | 27 ± 4 | 79 ± 13 * | n.d. |
Anti-inflammatory Cytokines | |||
IL-4 | n.d. | n.d. | n.d. |
IL-10 | 3659 ± 394 | 1018 ± 238 * | 5138 ± 651 *,$ |
Immunostimulatory Cytokines | |||
Eotaxin | 34 ± 12 | 49 ± 17 | 33 ± 18 |
IL-1α | n.d. | 7.8 ± 3.6 | n.d. |
IL-2 | 6.2 ± 4.9 | 6.6 ± 3.1 | 5.9 ± 2.7 |
IL-5 | n.d. | n.d. | n.d. |
IL-6 | 216 ± 68 | 582 ± 91 * | 114 ± 73 $ |
IL-12(p40) | 673 ± 116 | 803 ± 132 | 754 ± 82 |
IL-12(p70) | 256 ± 59 | 298 ± 102 | 272 ± 73 |
IL-13 | 12.1 ± 2.7 | 39.4 ± 8.3 * | 11.9 ± 3.7 |
Chemoattractants | |||
RANTES | 1042 ± 287 | 2365 ± 397 * | 1246 ± 231 $ |
MIP-1α | 127 ± 37 | 496 ± 82 * | 94 ± 21 $ |
MIP-1β | 214 ± 47 | 726 ± 54 * | 376 ± 97 $ |
MCP-1 | 184 ± 39 | 212 ± 42 | 206 ± 58 |
KC | 17 ± 4 | 15 ± 5 | 22 ± 7 |
Growth Factors/Cell differentiation factors | |||
IL-9 | n.d. | n.d. | n.d. |
IL-3 | 2673 ± 538 | 3982 ± 537 * | 698 ± 269 *,$ |
GM-CSF | 22 ± 7 | 38 ± 9 | 32 ± 9 |
KC | 17 ± 4 | 15 ± 5 | 22 ± 7 |
G-CSF | 513 ± 97 | 583 ± 104 | 638 ± 96 |
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Khandekar, D.; Dahunsi, D.O.; Manzanera Esteve, I.V.; Reid, S.; Rathmell, J.C.; Titze, J.; Tiriveedhi, V. Low-Salt Diet Reduces Anti-CTLA4 Mediated Systemic Immune-Related Adverse Events while Retaining Therapeutic Efficacy against Breast Cancer. Biology 2022, 11, 810. https://doi.org/10.3390/biology11060810
Khandekar D, Dahunsi DO, Manzanera Esteve IV, Reid S, Rathmell JC, Titze J, Tiriveedhi V. Low-Salt Diet Reduces Anti-CTLA4 Mediated Systemic Immune-Related Adverse Events while Retaining Therapeutic Efficacy against Breast Cancer. Biology. 2022; 11(6):810. https://doi.org/10.3390/biology11060810
Chicago/Turabian StyleKhandekar, Durga, Debolanle O. Dahunsi, Isaac V. Manzanera Esteve, Sonya Reid, Jeffrey C. Rathmell, Jens Titze, and Venkataswarup Tiriveedhi. 2022. "Low-Salt Diet Reduces Anti-CTLA4 Mediated Systemic Immune-Related Adverse Events while Retaining Therapeutic Efficacy against Breast Cancer" Biology 11, no. 6: 810. https://doi.org/10.3390/biology11060810
APA StyleKhandekar, D., Dahunsi, D. O., Manzanera Esteve, I. V., Reid, S., Rathmell, J. C., Titze, J., & Tiriveedhi, V. (2022). Low-Salt Diet Reduces Anti-CTLA4 Mediated Systemic Immune-Related Adverse Events while Retaining Therapeutic Efficacy against Breast Cancer. Biology, 11(6), 810. https://doi.org/10.3390/biology11060810