{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T16:38:46Z","timestamp":1777480726635,"version":"3.51.4"},"reference-count":39,"publisher":"SAGE Publications","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CBM"],"published-print":{"date-parts":[[2023,9,5]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3233\/cbm-230047","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T12:34:13Z","timestamp":1691152453000},"page":"103-110","source":"Crossref","is-referenced-by-count":1,"title":["TRB CDR3-cancer testis antigen chemical complementarity scoring for identifying productive immune responses in renal cell carcinoma"],"prefix":"10.1177","volume":"38","author":[{"given":"Tabitha R.","family":"Hudock","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vayda R.","family":"Barker","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon J.","family":"Manley","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Chobrutskiy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Oregon Health and Science University Hospital, Portland, OR, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boris I.","family":"Chobrutskiy","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Oregon Health and Science University Hospital, Portland, OR, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Diaz","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna J.","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Blanck","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA"},{"name":"Department of Immunology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"key":"10.3233\/CBM-230047_ref1","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1158\/2159-8290.CD-20-1559","article-title":"Tracking Cancer Evolution through the Disease Course","volume":"11","author":"Bailey","year":"2021","journal-title":"Cancer Discovery"},{"key":"10.3233\/CBM-230047_ref2","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.ccell.2021.02.013","article-title":"Progressive immune dysfunction with advancing disease stage in renal cell carcinoma","volume":"39","author":"Braun","year":"2021","journal-title":"Cancer Cell"},{"key":"10.3233\/CBM-230047_ref3","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1111\/cei.13567","article-title":"Reconnaissance of tumor immune microenvironment spatial heterogeneity in metastatic renal cell carcinoma and correlation with immunotherapy response","volume":"204","author":"Hajiran","year":"2021","journal-title":"Clinical and Experimental Immunology"},{"key":"10.3233\/CBM-230047_ref4","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1158\/2159-8290.CD-19-0499","article-title":"Tumor Microenvironment Dynamics in Clear-Cell Renal Cell Carcinoma","volume":"9","author":"Vuong","year":"2019","journal-title":"Cancer Discovery"},{"key":"10.3233\/CBM-230047_ref5","doi-asserted-by":"crossref","first-page":"762120","DOI":"10.3389\/fimmu.2021.762120","article-title":"Immunogenomic Analyses of the Prognostic Predictive Model for Patients With Renal Cancer","volume":"12","author":"Feng","year":"2021","journal-title":"Frontiers in Immunology"},{"key":"10.3233\/CBM-230047_ref6","doi-asserted-by":"crossref","first-page":"639636","DOI":"10.3389\/fimmu.2021.639636","article-title":"Current Advance of Immune Evasion Mechanisms and Emerging Immunotherapies in Renal Cell Carcinoma","volume":"12","author":"Jian","year":"2021","journal-title":"Frontiers in Immunology"},{"key":"10.3233\/CBM-230047_ref7","doi-asserted-by":"crossref","first-page":"100030","DOI":"10.1016\/j.esmoop.2020.100030","article-title":"First-line treatment of metastatic clear cell renal cell carcinoma: a decision-making analysis among experts","volume":"6","author":"Aeppli","year":"2021","journal-title":"ESMO Open"},{"key":"10.3233\/CBM-230047_ref8","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1158\/1535-7163.MCT-17-1299","article-title":"Resistance to Systemic Therapies in Clear Cell Renal Cell Carcinoma: Mechanisms and Management Strategies","volume":"17","author":"Makhov","year":"2018","journal-title":"Mol Cancer Ther"},{"key":"10.3233\/CBM-230047_ref9","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.molimm.2021.02.026","article-title":"High-throughput, sliding-window algorithm for assessing chemical complementarity between immune receptor CDR3 domains and cancer mutant peptides: TRG-PIK3CA interactions and breast cancer","volume":"135","author":"Chobrutskiy","year":"2021","journal-title":"Molecular Immunology"},{"key":"10.3233\/CBM-230047_ref10","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1038\/s41388-019-1101-2","article-title":"Chemical complementarity between immune receptor CDR3s and IDH1 mutants correlates with increased survival for lower grade glioma","volume":"39","author":"Chobrutskiy","year":"2020","journal-title":"Oncogene"},{"key":"10.3233\/CBM-230047_ref11","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1158\/0008-5472.CAN-21-1747","article-title":"Quantification of T- and B-cell Immune Receptor Distribution Diversity Characterizes Immune Cell Infiltration and Lymphocyte Heterogeneity in Clear Cell Renal Cell Carcinoma","volume":"82","author":"Ferrall-Fairbanks","year":"2022","journal-title":"Cancer Research"},{"key":"10.3233\/CBM-230047_ref12","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4137\/CIN.S35784","article-title":"Detection of Productively Rearranged TcR-alpha V-J Sequences in TCGA Exome Files: Implications for Tumor Immunoscoring and Recovery of Antitumor T-cells","volume":"15","author":"Gill","year":"2016","journal-title":"Cancer Inform"},{"key":"10.3233\/CBM-230047_ref13","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1080\/21645515.2016.1246095","article-title":"Identification of immunoglobulin V(D)J recombinations in solid tumor specimen exome files: Evidence for high level B-cell infiltrates in breast cancer","volume":"13","author":"Tong","year":"2017","journal-title":"Human Vaccines & Immunotherapeutics"},{"key":"10.3233\/CBM-230047_ref14","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s11060-018-03001-1","article-title":"Recovery of T-cell receptor V(D)J recombination reads from lower grade glioma exome files correlates with reduced survival and advanced cancer grade","volume":"140","author":"Chobrutskiy","year":"2018","journal-title":"J Neurooncol"},{"key":"10.3233\/CBM-230047_ref15","doi-asserted-by":"crossref","first-page":"e814","DOI":"10.1016\/j.immuni.2018.03.023","article-title":"The Immune Landscape of Cancer","volume":"48","author":"Thorsson","year":"2018","journal-title":"Immunity"},{"key":"10.3233\/CBM-230047_ref16","first-page":"1","article-title":"Chemical complementarity between immune receptor CDR3s and candidate cancer antigens correlating with reduced survival: evidence for outcome mitigation with corticosteroid treatments","author":"Patel","year":"2022","journal-title":"J Biomol Struct Dyn"},{"key":"10.3233\/CBM-230047_ref17","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.molimm.2022.08.001","article-title":"Chemical complementarity between tumor resident, T-cell receptor CDR3s and MAGEA3\/6 correlates with increased melanoma survival: Potential relevance to MAGE vaccine auto-reactivity","volume":"150","author":"Eakins","year":"2022","journal-title":"Molecular Immunology"},{"key":"10.3233\/CBM-230047_ref18","doi-asserted-by":"crossref","unstructured":"T.I. Huda, M.J. Diaz, E.C. Gozlan, A. Chobrutskiy, B.I. Chobrutskiy and G. Blanck, Immunogenomics Parameters for Patient Stratification in Alzheimer\u2019s Disease, J Alzheimers Dis (2022).","DOI":"10.3233\/JAD-220119"},{"key":"10.3233\/CBM-230047_ref19","doi-asserted-by":"crossref","first-page":"D816","DOI":"10.1093\/nar\/gkn673","article-title":"CTdatabase: a knowledge-base of high-throughput and curated data on cancer-testis antigens","volume":"37","author":"Almeida","year":"2009","journal-title":"Nucleic Acids Research"},{"key":"10.3233\/CBM-230047_ref20","first-page":"1","article-title":"Specific HLA alleles, paired with TCR V- and J-gene segment usage, link to distinct multiple myeloma survival rates","author":"Huda","year":"2021","journal-title":"Leukemia & Lymphoma"},{"key":"10.3233\/CBM-230047_ref21","first-page":"1","article-title":"Electrostatic Complementarity of T-Cell Receptor-Alpha CDR3 Domains and Mutant Amino Acids Is Associated with Better Survival Rates for Sarcomas","author":"Yeagley","year":"2021","journal-title":"Pediatr Hematol Oncol"},{"key":"10.3233\/CBM-230047_ref22","doi-asserted-by":"crossref","first-page":"101069","DOI":"10.1016\/j.tranon.2021.101069","article-title":"Chemical complementarity between immune receptors and cancer mutants, independent of antigen presentation protein binding, is associated with increased survival rates","volume":"14","author":"Hsiang","year":"2021","journal-title":"Transl Oncol"},{"key":"10.3233\/CBM-230047_ref23","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/s41423-019-0328-8","article-title":"Electrostatic complementarity of B-cell receptor CDR3s and TP53-mutant amino acids in breast cancer is associated with increased disease-free survival rates","volume":"17","author":"Arturo","year":"2020","journal-title":"Cell Mol Immunol"},{"key":"10.3233\/CBM-230047_ref24","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/imm.13165","article-title":"A scoring system for the electrostatic complementarities of T-cell receptors and cancer-mutant amino acids: multi-cancer analyses of associated survival rates","volume":"159","author":"Chobrutskiy","year":"2020","journal-title":"Immunology"},{"key":"10.3233\/CBM-230047_ref25","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s00432-018-2815-1","article-title":"T-cell receptor-alpha CDR3 domain chemical features correlate with survival rates in bladder cancer","volume":"145","author":"Chobrutskiy","year":"2019","journal-title":"Journal of Cancer Research and Clinical Oncology"},{"key":"10.3233\/CBM-230047_ref26","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/iji.12550","article-title":"A comparison of immune receptor recombination databases sourced from tumour exome or RNAseq files: Verifications of immunological distinctions between primary and metastatic melanoma","volume":"48","author":"Patel","year":"2021","journal-title":"Int J Immunogenet"},{"key":"10.3233\/CBM-230047_ref27","doi-asserted-by":"crossref","first-page":"101684","DOI":"10.1016\/j.jbc.2022.101684","article-title":"T cell receptors employ diverse strategies to target a p53 cancer neoantigen","volume":"298","author":"Wu","year":"2022","journal-title":"The Journal of Biological Chemistry"},{"key":"10.3233\/CBM-230047_ref28","doi-asserted-by":"crossref","first-page":"17291","DOI":"10.1038\/s41598-019-53756-4","article-title":"Single variable domains from the T cell receptor beta chain function as mono- and bifunctional CARs and TCRs","volume":"9","author":"Oh","year":"2019","journal-title":"Scientific Reports"},{"key":"10.3233\/CBM-230047_ref29","doi-asserted-by":"crossref","first-page":"587756","DOI":"10.3389\/fimmu.2020.587756","article-title":"A Conserved TCRbeta Signature Dominates a Highly Polyclonal T-Cell Expansion During the Acute Phase of a Murine Malaria Infection","volume":"11","author":"Smith","year":"2020","journal-title":"Frontiers in Immunology"},{"key":"10.3233\/CBM-230047_ref30","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/s12859-021-04087-7","article-title":"Clustering based approach for population level identification of condition-associated T-cell receptor beta-chain CDR3 sequences","volume":"22","author":"Yohannes","year":"2021","journal-title":"BMC Bioinformatics"},{"key":"10.3233\/CBM-230047_ref31","doi-asserted-by":"crossref","first-page":"e9416","DOI":"10.15252\/msb.20199416","article-title":"Predicting antigen specificity of single T cells based on TCR CDR3 regions","volume":"16","author":"Fischer","year":"2020","journal-title":"Mol Syst Biol"},{"key":"10.3233\/CBM-230047_ref32","doi-asserted-by":"crossref","first-page":"664514","DOI":"10.3389\/fimmu.2021.664514","article-title":"Contribution of T Cell Receptor Alpha and Beta CDR3, MHC Typing, V and J Genes to Peptide Binding Prediction","volume":"12","author":"Springer","year":"2021","journal-title":"Frontiers in Immunology"},{"key":"10.3233\/CBM-230047_ref33","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/JLB.6COVCRA1120-762R","article-title":"TRB sequences targeting ORF1a\/b are associated with disease severity in hospitalized COVID-19 patients","volume":"111","author":"Assmann","year":"2022","journal-title":"Journal of Leukocyte Biology"},{"key":"10.3233\/CBM-230047_ref34","doi-asserted-by":"crossref","first-page":"280","DOI":"10.4049\/jimmunol.165.1.280","article-title":"Altered peptide ligand-mediated TCR antagonism can be modulated by a change in a single amino acid residue within the CDR3 beta of an MHC class I-restricted TCR","volume":"165","author":"Kalergis","year":"2000","journal-title":"Journal of Immunology"},{"key":"10.3233\/CBM-230047_ref35","doi-asserted-by":"crossref","unstructured":"V.R. Barker, M. Varkhedi, D.N. Patel, M. Hsiang, A. Chobrutskiy, B.I. Chobrutskiy and G. Blanck, TCR CDR3-antigen chemical complementarity associated with poor ovarian cancer outcomes: A vestigial immune response to early cancer antigens? Am J Reprod Immunol, (2022).","DOI":"10.1111\/aji.13639"},{"key":"10.3233\/CBM-230047_ref36","doi-asserted-by":"crossref","first-page":"4338","DOI":"10.1038\/s41598-021-83767-z","article-title":"Immune classification of clear cell renal cell carcinoma","volume":"11","author":"Su","year":"2021","journal-title":"Scientific Reports"},{"key":"10.3233\/CBM-230047_ref37","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/s13046-022-02397-z","article-title":"The immune landscape of solid pediatric tumors","volume":"41","author":"Sherif","year":"2022","journal-title":"J Exp Clin Cancer Res"},{"key":"10.3233\/CBM-230047_ref38","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.18632\/aging.102746","article-title":"Identification of an immune-related risk signature for predicting prognosis in clear cell renal cell carcinoma","volume":"12","author":"Hua","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"10.3233\/CBM-230047_ref39","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1007\/s00345-018-2309-4","article-title":"Prognostic factors and prognostic models for renal cell carcinoma: a literature review","volume":"36","author":"Klatte","year":"2018","journal-title":"World J Urol"}],"container-title":["Cancer Biomarkers"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/CBM-230047","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:10:17Z","timestamp":1777385417000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/CBM-230047"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,5]]},"references-count":39,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.3233\/cbm-230047","relation":{},"ISSN":["1875-8592","1574-0153"],"issn-type":[{"value":"1875-8592","type":"electronic"},{"value":"1574-0153","type":"print"}],"subject":[],"published":{"date-parts":[[2023,9,5]]}}}