Affiliations: [a] Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA | [b] Department of Genitourinary Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA | [c] Department of Pediatrics, Oregon Health and Science University Hospital, Portland, OR, USA | [d] Department of Internal Medicine, Oregon Health and Science University Hospital, Portland, OR, USA | [e] Department of Immunology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
Correspondence:
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Corresponding author: George Blanck, Department of Molecular Medicine, Morsani College of Medicine, 12901 Bruce B. Downs Bd., MDC7 Tampa, FL 33612, USA. E-mail: [email protected].
Abstract: 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.
Keywords: Renal cell carcinoma, chemical complementarity, immune signature genes, TRB CDR3 Interactions with cancer testis antigens
