Identification of tumor-reactive B cells and systemic IgG in breast cancer based on clonal frequency in the sentinel lymph node

Jonathan R. McDaniel, Stephanie C. Pero, William N. Voss, Girja S. Shukla, Yujing Sun, Sebastian Schaetzle, Chang Han Lee, Andrew P. Horton, Seth Harlow, Jimmy Gollihar, Jared W. Ellefson, Christopher C. Krag, Yuri Tanno, Nikoletta Sidiropoulos, George Georgiou, Gregory C. Ippolito, David N. Krag

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

A better understanding of antitumor immune responses is the key to advancing the field of cancer immunotherapy. Endogenous immunity in cancer patients, such as circulating anticancer antibodies or tumor-reactive B cells, has been historically yet incompletely described. Here, we demonstrate that tumor-draining (sentinel) lymph node (SN) is a rich source for tumor-reactive B cells that give rise to systemic IgG anticancer antibodies circulating in the bloodstream of breast cancer patients. Using a synergistic combination of high-throughput B-cell sequencing and quantitative immunoproteomics, we describe the prospective identification of tumor-reactive SN B cells (based on clonal frequency) and also demonstrate an unequivocal link between affinity-matured expanded B-cell clones in the SN and antitumor IgG in the blood. This technology could facilitate the discovery of antitumor antibody therapeutics and conceivably identify novel tumor antigens. Lastly, these findings highlight the unique and specialized niche the SN can fill in the advancement of cancer immunotherapy.

Original languageEnglish (US)
Pages (from-to)729-738
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume67
Issue number5
DOIs
StatePublished - May 1 2018

Keywords

  • Antibody
  • Breast cancer
  • Heavy–light (VH:VL) chain pairing
  • Next-Generation Sequencing
  • Repertoire
  • Sentinel Node

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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