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

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Abbreviations

BCR:

B-cell receptor

BRCA:

Breast cancer

DFS:

Disease-free survival

ER:

Estrogen receptor

GDC:

Genomic data commons

HLA:

human leukocyte antigen

IGH:

Immunoglobulin heavy gene

IGK:

Immunoglobulin kappa gene

IGL:

immunoglobulin lambda gene

IMGT:

ImmunoGeneTics organization

KM:

Kaplan–Meier

OS:

Overall survival

PR:

Progesterone receptor

TCGA:

The cancer genome atlas

TIL:

Tumor-infiltrating lymphocyte

TCR:

T-cell receptor

TNBC:

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

TRA:

T-cell receptor alpha gene

TRB:

T-cell receptor beta gene

TRG:

T-cell receptor gamma gene

TRD:

T-cell receptor delta gene

WXS:

Whole exome file

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Acknowledgements

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

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Authors and Affiliations

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

    Wei Lue Tong, Blake M. Callahan, Yaping N. Tu, Saif Zaman, Boris I. Chobrutskiy & George Blanck

  2. Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, 12901 Bruce B. Downs Blvd., Tampa, FL, 33612, USA

    George Blanck

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  1. Wei Lue Tong
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  2. Blake M. Callahan
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Correspondence to George Blanck.

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Tong, W.L., Callahan, B.M., Tu, Y.N. et al. Immune receptor recombinations from breast cancer exome files, independently and in combination with specific HLA alleles, correlate with better survival rates. Breast Cancer Res Treat 173, 167–177 (2019). https://doi.org/10.1007/s10549-018-4961-1

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