TY - JOUR
T1 - Identification of tumor-reactive B cells and systemic IgG in breast cancer based on clonal frequency in the sentinel lymph node
AU - McDaniel, Jonathan R.
AU - Pero, Stephanie C.
AU - Voss, William N.
AU - Shukla, Girja S.
AU - Sun, Yujing
AU - Schaetzle, Sebastian
AU - Lee, Chang Han
AU - Horton, Andrew P.
AU - Harlow, Seth
AU - Gollihar, Jimmy
AU - Ellefson, Jared W.
AU - Krag, Christopher C.
AU - Tanno, Yuri
AU - Sidiropoulos, Nikoletta
AU - Georgiou, George
AU - Ippolito, Gregory C.
AU - Krag, David N.
N1 - Funding Information:
Funding This study was supported by S.D. Ireland Cancer Research Foundation (David N. Krag), The Lake Champlain Cancer Research Foundation Grant (Stephanie C. Pero, Nikoletta Sidiropoulos), the Defense Threat Reduction Agency (DTRA) HDTRA1-12-C-0105 (George Georgiou), and the National Institutes of Health (NIH) 5R21AI119368 (Gregory C. Ippolito). The Zeiss 510 META laser scanning confocal microscope was supported by NIH Award Number 1S10RR019246 from the National Center for Research Resources.
Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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.
AB - 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.
KW - Antibody
KW - Breast cancer
KW - Heavy–light (VH:VL) chain pairing
KW - Next-Generation Sequencing
KW - Repertoire
KW - Sentinel Node
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U2 - 10.1007/s00262-018-2123-2
DO - 10.1007/s00262-018-2123-2
M3 - Article
C2 - 29427082
AN - SCOPUS:85041801256
SN - 0340-7004
VL - 67
SP - 729
EP - 738
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 5
ER -