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  • Poster presentation
  • Open Access

Discovery and characterization of an immunogenic neoantigen in a patient with metastatic triple negative breast cancer

  • 1,
  • 2,
  • 3,
  • 4,
  • 5,
  • 6,
  • 6,
  • 6,
  • 6,
  • 5,
  • 5 and
  • 6
Journal for ImmunoTherapy of Cancer20153 (Suppl 2) :P284

https://doi.org/10.1186/2051-1426-3-S2-P284

  • Published:

Keywords

  • Breast Cancer
  • Notch Signaling
  • Triple Negative Breast Cancer
  • Tumor Infiltrate Lymphocyte
  • Notch Signaling Pathway

A growing body of evidence suggests that successful clinical immunotherapy may depend on mutation-specific T cell responses. Using whole-exome and RNA sequencing of a resected metastatic deposit from a patient with triple-negative (ER-, PR-, Her2 non-amplified) breast cancer, we identified 72 non-synonymous mutations. Using previously published methods of autologous antigen presentation[1], we identified a novel non-synonymous mutation in a regulator of the Notch signaling pathway, RBPJ (recombination signal binding protein for immunoglobulin kappa J region), that encodes a neoantigen specifically recognized by autologous CD4+ tumor infiltrating lymphocytes. Antigen recognition was restricted by the Class II DR locus. Deep sequencing or PCR of all 16 metastases collected at autopsy revealed that the mutation was ubiquitously present in all samples. To the best of our knowledge, this represents the first report of an immunogenic mutation in breast cancer.

Authors’ Affiliations

(1)
George Washington University, Washington, DC, USA
(2)
Surgery Branch, NIH/NCI, Bethesda, MD, USA
(3)
Rutgers Robert Wood Johnson Medical School, NCI/NIH, New Brunswick, NJ, USA
(4)
NCI/NIH, Bethesda, MD, USA
(5)
Surgery Branch/National Cancer Institute/National Institutes of Health, Bethesda, MD, USA
(6)
NIH/NCI, Bethesda, MD, USA

References

  1. Tran E, Turcotte S, Gros A, et al: Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 2014, 344: 641-5.PubMedView ArticleGoogle Scholar

Copyright

© Assadipour et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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