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T-cell receptor-β V and J usage, in combination with particular HLA class I and class II alleles, correlates with cancer survival patterns

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Abstract

Class I and class II HLA proteins, respectively, have been associated with subsets of V(D)J usage resulting from recombination of the T-cell receptor (TCR) genes. Additionally, particular HLA alleles, in combination with dominant TCR V(D)J recombinations, have been associated with several autoimmune diseases. The recovery of TCR recombination reads from tumor specimen exome files has allowed rapid and extensive assessments of V(D)J usage, likely for cancer resident T-cells, across relatively large cancer datasets. The results from this approach, in this report, have permitted an extensive alignment of TCR-β VDJ usage and HLA class I and II alleles. Results indicate the correlation of both better and worse cancer survival rates with particular TCR-β, V and J usage-HLA allele combinations, with differences in median survival times ranging from 7 to 130 months, depending on the cancer and the specific TCR-β V and J usage/HLA class allele combination.

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Abbreviations

CDR3:

Complementarity determining region-3

dbGaP:

Database of genotypes and phenotypes

HLA:

Human leukocyte antigen

HNSC:

Head and neck cancer

LUAD:

Lung adenocarcinoma

KM:

Kaplan–Meier

NKT:

Natural killer T-cell

OV:

Ovarian cancer

SKCM:

Skin, cutaneous melanoma

SPSS:

Statistical package for the social sciences

STAD:

Stomach adenocarcinoma

TCGA:

The cancer genome atlas

TCR:

T-cell receptor

WXS:

Whole exome sequence

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Acknowledgements

Authors would like to acknowledge the support of University of South Florida research computing. The whole exome files for this project were made available via database of Genotypes and Phenotypes approved project #6300, to George Blanck.

Funding

This work was supported by the taxpayers of the State of Florida. Blake M. Callahan was a recipient of a Bonati research stipend.

Author information

Authors and Affiliations

  1. Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Bd. MDC7, Tampa, FL, 33612, USA

    Blake M. Callahan, John M. Yavorski, Yaping N. Tu, Wei Lue Tong, Jacob C. Kinskey, Kendall R. Clark & George Blanck

  2. Research Computing, University of South Florida, Tampa, USA

    Timothy J. Fawcett

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

    George Blanck

Authors
  1. Blake M. Callahan
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  2. John M. Yavorski
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  3. Yaping N. Tu
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  4. Wei Lue Tong
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  5. Jacob C. Kinskey
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  6. Kendall R. Clark
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  7. Timothy J. Fawcett
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  8. George Blanck
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Contributions

Blake M. Callahan contributed to the design of the project and conducted most of the original, basic assessment of TCR and HLA combinations in the whole exome files; and contributed to manuscript preparation. Blake M. Callahan, John M. Yavorski, and Jacob C. Kinskey contributed extensively to the KM analyses. Yaping N. Tu, Wei Lue Tong and Timothy J. Fawcett contributed extensively to the code-writing and use of USF research computing. Kendall R. Clark contributed TCR data for a subset of cancer types. George Blanck contributed to the design of the project, supervised the project, and participated extensively in manuscript preparation.

Corresponding author

Correspondence to George Blanck.

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Callahan, B.M., Yavorski, J.M., Tu, Y.N. et al. T-cell receptor-β V and J usage, in combination with particular HLA class I and class II alleles, correlates with cancer survival patterns. Cancer Immunol Immunother 67, 885–892 (2018). https://doi.org/10.1007/s00262-018-2139-7

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  • DOI: https://doi.org/10.1007/s00262-018-2139-7

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