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Immunity against cancer cells may promote their proliferation and metastasis

Title
Immunity against cancer cells may promote their proliferation and metastasis
Authors
Lin, Chih-WeiXie, JiaZhang, DingHan, Kyung HoGrande, GeramieWu, Nicholas C.Yang, ZhuoYea, KyungmooLerner, Richard A.
DGIST Authors
Lin, Chih-Wei; Xie, Jia; Zhang, Ding; Han, Kyung Ho; Grande, Geramie; Wu, Nicholas C.; Yang, Zhuo; Yea, Kyungmoo; Lerner, Richard A.
Issue Date
2020-01
Citation
Proceedings of the National Academy of Sciences of the United States of America, 117(1), 426-431
Type
Article
Article Type
Article
Author Keywords
agonistantibodycancer
Keywords
TRKBMUTATIONSEMTAUTOANTIBODIESANTIBODIESTRANSITIONOVARIAN
ISSN
0027-8424
Abstract
Herein we present a concept in cancer where an immune response is detrimental rather than helpful. In the cancer setting, the immune system is generally considered to be helpful in curtailing the initiation and progression of tumors. In this work we show that a patient’s immune response to their tumor can, in fact, either enhance or inhibit tumor cell growth. Two closely related autoantibodies to the growth factor receptor TrkB were isolated from cancer patients’ B cells. Although highly similar in sequence, one antibody was an agonist while the other was an antagonist. The agonist antibody was shown to increase breast cancer cell growth both in vitro and in vivo, whereas the antagonist antibody inhibited growth. From a mechanistic point of view, we showed that binding of the agonist antibody to the TrkB receptor was functional in that it initiated downstream signaling identical to its natural growth factor ligand, brain-derived neurotrophic factor (BDNF). Our study shows that individual autoantibodies may play a role in cancer patients. © 2020 National Academy of Sciences. All rights reserved.
URI
http://hdl.handle.net/20.500.11750/11425
DOI
10.1073/pnas.1916833117
Publisher
National Academy of Sciences
Related Researcher
  • Author Yea, Kyungmoo Protein Engineering Lab
  • Research Interests Antibody, Engineering, Phage Display, Therapeutics, Immune, Exosome, Translational, Cytokine
Files:
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Collection:
Department of New BiologyProtein Engineering Lab1. Journal Articles


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