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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
TRB CDR3-cancer testis antigen chemical complementarity scoring for identifying productive immune responses in renal
Tabitha R Hudock1, Vayda R Barker1, Brandon J Manley2
1Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Background:
Immunogenomics approaches to the characterization of renal cell carcinoma (RCC) have helped to better our understanding of the features of RCC immune dysfunction. However, much is still unknown with regard to specific immune interactions and their impact in the tumor microenvironment.
Objective:
This study applied chemical complementarity scoring for the TRB complementarity determining region-3 (CDR3) amino acid sequences and cancer testis antigens (CTAs) to determine whether such complementarity correlated with survival and the expression of immune marker genes.
Methods:
TRB recombination reads from RCC tumor samples from RNAseq files obtained from two separate databases, Moffitt Cancer Center and The Cancer Genome Atlas (TCGA), were evaluated. Chemical complementarity scores (CSs) were calculated for TRB CDR3-CTA pairs and survival assessments based on those CSs were performed.
Results:
Moffitt Cancer Center and TCGA cases representing the upper 50th percentile of chemical CSs for TRB CDR3 amino acid sequences and the CTA POTEA were found to be associated with a better overall survival (OS) Also, greater tumor RNA expression of multiple immune signature genes, including granzyme A, granzyme B, and interferon-gamma were correlated with the higher chemical CSs.
Conclusions:
These results indicate that TRB CDR3-CTA chemical complementarity scoring may be useful in distinguishing RCC cases with a productive, anti-tumor immune response from cases where basic immune parameter assessments are inconsistent with a productive immune response.
Insights
Chemical complementarity scoring of T-cell receptor beta (TRB) complementarity determining region-3 (CDR3) amino acid sequences and cancer testis antigens (CTAs) may predict better survival in renal cell carcinoma (RCC) patients. Higher scores correlated with increased expression of immune marker genes.
Area of Science:
- Immunogenomics
- Oncology
- Molecular Biology
Background:
- Renal cell carcinoma (RCC) immunogenomics reveals immune dysfunction, but specific tumor microenvironment interactions remain unclear.
- Understanding immune cell interactions is crucial for RCC treatment strategies.
Purpose of the Study:
- To investigate the correlation between chemical complementarity scoring of TRB CDR3 amino acid sequences and cancer testis antigens (CTAs).
- To assess if this complementarity impacts patient survival and immune marker gene expression in RCC.
Main Methods:
- TRB recombination reads from RCC tumor samples were analyzed from Moffitt Cancer Center and The Cancer Genome Atlas (TCGA) databases.
- Chemical complementarity scores (CSs) were calculated for TRB CDR3-CTA pairs.
- Survival assessments were performed based on calculated CSs.
Main Results:
- Higher chemical CSs for TRB CDR3 and the CTA POTEA were associated with better overall survival (OS) in both Moffitt and TCGA cohorts.
- Increased tumor RNA expression of immune signature genes (granzyme A, granzyme B, interferon-gamma) correlated with higher chemical CSs.
Conclusions:
- TRB CDR3-CTA chemical complementarity scoring can potentially differentiate RCC cases with productive anti-tumor immune responses.
- This scoring method may offer insights into immune response efficacy where basic assessments are inconsistent.
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