Electrostatic Complementarities of Glioblastoma-Resident T-Cell Receptors and Cancer Testis Antigens Linked to Poor Outcomes and High Levels of Sphingosine Kinase-2 Expression.

Autor:	Arias MA; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA., Cios KJ; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA., Kacsoh DB; College of Medicine, University of Central Florida, Orlando, FL 32827, USA., Montgomery BE; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA., Song JJ; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA., Patel AR; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA., Chobrutskiy A; Department of Pediatrics, Oregon Health and Science University Hospital, Portland, OR 97239, USA., Chobrutskiy BI; Internal Medicine, Oregon Health and Science University Hospital, Portland, OR 97239, USA., Blanck G; Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.; Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Jazyk:	angličtina
Zdroj:	Biology [Biology (Basel)] 2023 Apr 10; Vol. 12 (4). Date of Electronic Publication: 2023 Apr 10.
DOI:	10.3390/biology12040575
Abstrakt:	Introduction: Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. Despite a growing understanding of glioblastoma pathology, the prognosis remains poor. Methods: In this study, we used a previously extensively benchmarked algorithm to retrieve immune receptor (IR) recombination reads from GBM exome files available from the cancer genome atlas. The T-cell receptor complementarity determining region-3 (CDR3) amino acid sequences that represent the IR recombination reads were assessed and used for the generation of chemical complementarity scores (CSs) that represent potential binding interactions with cancer testis antigens (CTAs), which is an approach particularly suited to a big data setting. Results: The electrostatic CSs representing the TRA and TRB CDR3s and the CTAs, SPAG9, GAGE12E, and GAGE12F, indicated that an increased electrostatic CS was associated with worse disease-free survival (DFS). We also assessed the RNA expression of immune marker genes, which indicated that a high-level expression of SPHK2 and CIITA genes also correlated with high CSs and worse DFS. Furthermore, apoptosis-related gene expression was revealed to be lower when the TCR CDR3-CTA electrostatic CSs were high. Conclusion: Adaptive IR recombination reads from exome files have the potential to aid in GBM prognoses and may provide opportunities to detect unproductive immune responses.
Databáze:	MEDLINE
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