Breast Cancer Research and Treatment

, Volume 173, Issue 1, pp 167–177 | Cite as

Immune receptor recombinations from breast cancer exome files, independently and in combination with specific HLA alleles, correlate with better survival rates

  • Wei Lue Tong
  • Blake M. Callahan
  • Yaping N. Tu
  • Saif Zaman
  • Boris I. Chobrutskiy
  • George BlanckEmail author



Immune characterizations of cancers, including breast cancer, have led to information useful for prognoses and are considered to be important in the future of refining the use of immunotherapies, including immune checkpoint inhibitor therapies. In this study, we sought to extend these characterizations with genomics approaches, particularly with cost-effective employment of exome files.


By recovery of immune receptor recombination reads from the cancer genome atlas (TCGA) breast cancer dataset, we observed associations of these recombinations with T-cell and B-cell biomarkers and with distinct survival rates.


Recovery of TRD or IGH recombination reads was associated with an improved disease-free survival (p = 0.047 and 0.045, respectively). Determination of the HLA types using the exome files allowed matching of T-cell receptor V- and J-gene segment usage with specific HLA alleles, in turn allowing a refinement of the association of immune receptor recombination read recoveries with survival. For example, the TRBV7, HLA-C*07:01 combination represented a significantly worse, disease-free outcome (p = 0.014) compared to all other breast cancer samples. By direct comparisons of distinct TRB gene segment usage, HLA allele combinations revealed breast cancer subgroups, within the entire TCGA breast cancer dataset with even more dramatic survival distinctions.


In sum, the use of exome files for recovery of adaptive immune receptor recombination reads, and the simultaneous determination of HLA types, has the potential of advancing the use of immunogenomics for immune characterization of breast tumor samples.


Breast cancer Immune receptor recombinations V- and J-gene segment usage HLA alleles 



B-cell receptor


Breast cancer


Disease-free survival


Estrogen receptor


Genomic data commons


human leukocyte antigen


Immunoglobulin heavy gene


Immunoglobulin kappa gene


immunoglobulin lambda gene


ImmunoGeneTics organization




Overall survival


Progesterone receptor


The cancer genome atlas


Tumor-infiltrating lymphocyte


T-cell receptor


Triple-negative breast cancer (negative for ER, PR, and HER2)


T-cell receptor alpha gene


T-cell receptor beta gene


T-cell receptor gamma gene


T-cell receptor delta gene


Whole exome file



Authors gratefully acknowledge the support of USF research computing and the taxpayers of the State of Florida. This study is dedicated to Frances.

Compliance with ethical standards

Conflict of interest

Authors have nothing to declare.

Research involving human participants and/or animals

Not applicable. (non-human subjects research).

Informed consent

Not applicable.

Supplementary material

10549_2018_4961_MOESM1_ESM.pdf (2.3 mb)
Supplementary material 1 (PDF 2396 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Molecular MedicineMorsani College of Medicine, University of South FloridaTampaUSA
  2. 2.Department of ImmunologyH. Lee Moffitt Cancer Center and Research InstituteTampaUSA

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