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Tumor resident, TRA anti-viral CDR3 chemical sequence motifs are associated with a better breast cancer outcome

Genes & Immunity volume 24, pages 92–98 (2023)Cite this article

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Abstract

While for certain cancers, such as cervical cancer, the link to viral infections is very strong and very clear, other cancers represent a history of links to viral infections that are either co-morbidities or drive the cancer in ways that are not yet fully understood, for example the “hit and run” possibility. To further understand the connection of viral infections and the progress of breast cancer, we identified the chemical features of known anti-viral, T-cell receptor alpha chain (TRA) complementarity determining region-3 (CDR3) amino acid sequences among the CDR3s of breast cancer patient TRA recombinations and assessed the association of those features with patient outcomes. The application of this novel paradigm indicated consistent associations of tumor-derived, anti-CMV CDR3 chemical sequence motifs with better breast cancer patient outcomes but did not indicate an opportunity to establish risk stratifications for other cancer types. Interestingly, breast cancer samples with no detectable TRA recombinations represented a better outcome than samples with the non-anti-CMV CDR3s, further adding to a rapidly developing series of results allowing a distinction between positive and possibly harmful cancer immune responses.

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Fig. 1
Fig. 2: KM overall survival (OS) and disease-free survival (DFS) analyses of BRCA case IDs with anti-CMV TRA CDR3 chemical sequence motifs in primary tumor samples.
Fig. 3: KM OS and DFS analyses of TCGA-CESC case IDs with anti-CMV TRA CDR3 chemical sequence motifs in tumor samples and for other control sets.
Fig. 4: KM analyses of BRCA case IDs with anti-viral TRA CDR3 chemical sequence motifs in tumor samples versus TRA-cold case IDs.

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Data availability

All data used in the analyses for this report are available in the SOM; and as publicly available information at cbioportal.org.

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Acknowledgements

Authors thank Ms. Corinne Walters for expert management of the administrative and legal aspects of the dataset access-approval process; USF research computing; and the taxpayers of the State of Florida.

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Authors and Affiliations

  1. Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, 33612, USA

    Michael J. Diaz, Dhruv N. Patel, Michelle Yeagley, Monica Hsiang & George Blanck

  2. College of Medicine, University of Central Florida, Orlando, FL, 32827, USA

    Dorottya B. Kacsoh

  3. Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA

    George Blanck

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Contributions

MJD: Conceptualization; Formal analysis; Methodology; Software; Visualization; Writing - review & editing.: DBK: Formal analysis; Methodology; Software. DNP: Formal analysis; Methodology; Software. MY: Formal analysis; Methodology. MH: Formal analysis; Methodology; Software. GB: Methodology; Project administration; Resources; Supervision; Writing - review & editing.

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Correspondence to George Blanck.

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The data used in this report were accessed via NIH dbGaP project approval number 6300. This report represents non-human subjects research, per the dbGaP approval, and as such, there is no consent to participate needed.

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Diaz, M.J., Kacsoh, D.B., Patel, D.N. et al. Tumor resident, TRA anti-viral CDR3 chemical sequence motifs are associated with a better breast cancer outcome. Genes Immun 24, 92–98 (2023). https://doi.org/10.1038/s41435-023-00201-2

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