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.