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01-05-2018 | Original Article

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

Authors: 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

Published in: Cancer Immunology, Immunotherapy | Issue 5/2018

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.

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Title: Identification of tumor-reactive B cells and systemic IgG in breast cancer based on clonal frequency in the sentinel lymph node
Authors: 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
Publication date: 01-05-2018
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 5/2018
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-018-2123-2

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