Improved Immunotherapy Outcomes via Cuproptosis Upregulation of HLA-DRA Expression: Promoting the Aggregation of CD4+ and CD8+T Lymphocytes in Clear Cell Renal Cell Carcinoma
Abstract
:1. Introduction
2. Results
2.1. Key Cuproptosis-Related Gene in ccRCC, HLA-DRA
2.2. HLA-DRA Expressed as an MHC-II in ccRCC Cell Lines and Pathological Tissues
2.3. High HLA-DRA Expression Enhances the Sensitivity of ccRCC to ICI Treatment
2.4. HLA-DRA Positively Affects the Immune Microenvironment of ccRCC
2.5. Cuproptosis Upregulates the Protein Expression of HLA-DRA from the Transcriptional Level in a Dose-Dependent Manner through Reactive Oxygen Species
2.6. Cuproptosis Improves the Outcomes of Anti-PD-1 Treatment In Vivo
2.7. Upregulated Expression of HLA-DRA via Cuproptosis Synergy with ICI Therapy: Enhanced Aggregation of CD4+ and CD8+ T Cells Associated with Increased Levels of CCL5, CXCL9, and CXCL10
3. Discussion
4. Materials and Methods
4.1. Data Collection and Screening of Cuproptosis-Related Genes (CRGs)
4.2. Functional Enrichment and Drug Sensitivity Analyses
4.3. Analysis of the Immune Microenvironment and Immune Infiltration of the Tumors
4.4. Cell Culture and Cell Lines
4.5. RNA Isolation and Quantitative Reverse-Transcription Polymerase Chain Reaction (qRT-PCR)
4.6. Western Blot Analysis
4.7. Cell Viability Assay
4.8. Cuproptosis Detection
4.9. Transcriptome Sequencing Analysis
4.10. Mouse Syngeneic Tumor Experiment
4.11. Flow Cytometry Detection
4.12. Immunohistochemical (IHC) Staining and Semi-Quantitative Scoring
4.13. Statistical Analysis
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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Wang, B.; Liu, Y.; Xiong, F.; Wang, C. Improved Immunotherapy Outcomes via Cuproptosis Upregulation of HLA-DRA Expression: Promoting the Aggregation of CD4+ and CD8+T Lymphocytes in Clear Cell Renal Cell Carcinoma. Pharmaceuticals 2024, 17, 678. https://doi.org/10.3390/ph17060678
Wang B, Liu Y, Xiong F, Wang C. Improved Immunotherapy Outcomes via Cuproptosis Upregulation of HLA-DRA Expression: Promoting the Aggregation of CD4+ and CD8+T Lymphocytes in Clear Cell Renal Cell Carcinoma. Pharmaceuticals. 2024; 17(6):678. https://doi.org/10.3390/ph17060678
Chicago/Turabian StyleWang, Bowen, Yiwen Liu, Feng Xiong, and Chunyang Wang. 2024. "Improved Immunotherapy Outcomes via Cuproptosis Upregulation of HLA-DRA Expression: Promoting the Aggregation of CD4+ and CD8+T Lymphocytes in Clear Cell Renal Cell Carcinoma" Pharmaceuticals 17, no. 6: 678. https://doi.org/10.3390/ph17060678