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The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
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Complement as Prognostic Biomarker and Potential Therapeutic Target in Renal Cell Carcinoma
Britney Reese1, Ashok Silwal1, Elizabeth Daugherity1
1Department of Immunotherapeutics and Biotechnology, School of Pharmacy, Texas Tech University Health Sciences Center, Abilene, TX 79601.
Journal of Immunology (Baltimore, Md. : 1950)
|November 7, 2020
Summary
Complement drives tumor growth, particularly in kidney cancer. Targeting complement may enhance immune responses and treat tumors resistant to immune checkpoint inhibitors.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Preclinical studies suggest the complement system promotes tumor growth.
- Identifying optimal targets for complement-based therapies in human malignancies is crucial.
Purpose of the Study:
- To investigate the role of complement in renal cell carcinoma (RCC) and its potential as a therapeutic target.
- To correlate complement gene/protein expression with clinical outcomes and immune cell infiltration in RCC.
- To evaluate the efficacy of complement blockade in a preclinical model of kidney cancer resistant to PD-1 blockade.
Main Methods:
- Analysis of complement gene expression in human RCC cohorts.
- Assessment of complement protein deposition in tumor tissues.
- Correlation of complement levels with tumor grade, subtype, and patient prognosis.
- Evaluation of complement blockade in a mouse model of kidney cancer.
Main Results:
- High expression of 11 complement genes associated with poor prognosis in RCC.
- Complement proteins found in tumor stroma, vasculature, and leukocytes, influencing the tumor microenvironment.
- Complement abundance correlated with higher nuclear grade and an aggressive inflammatory subtype of RCC.
- Plasma complement levels predicted response to immune checkpoint inhibitors.
- Complement blockade reduced tumor growth, enhanced anti-tumor immunity, and reduced angiogenesis in a resistant mouse model.
Conclusions:
- Complement plays a significant role in the immune landscape of renal cell carcinoma.
- Tumors resistant to immune checkpoint inhibitors may be potential candidates for complement-based therapies.
- Further investigation is warranted despite study limitations.
