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

Miguel A Arias; Konrad J Cios; Dorottya B Kacsoh; Bailey E Montgomery; Joanna J Song; Anishaa R Patel; Andrea Chobrutskiy; Boris I Chobrutskiy; George Blanck

doi:10.3390/biology12040575

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

Biology (Basel). 2023 Apr 10;12(4):575. doi: 10.3390/biology12040575.

Authors

Miguel A Arias¹, Konrad J Cios¹, Dorottya B Kacsoh², Bailey E Montgomery¹, Joanna J Song¹, Anishaa R Patel¹, Andrea Chobrutskiy³, Boris I Chobrutskiy⁴, George Blanck^{1

5}

Affiliations

¹ Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
² College of Medicine, University of Central Florida, Orlando, FL 32827, USA.
³ Department of Pediatrics, Oregon Health and Science University Hospital, Portland, OR 97239, USA.
⁴ Internal Medicine, Oregon Health and Science University Hospital, Portland, OR 97239, USA.
⁵ Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.

Abstract

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.

Keywords: adaptive immune receptors; cancer testis antigens; chemical complementarity scoring; glioblastoma; sphingosine kinase-2.

Grants and funding

This research received no external funding.