TNFα SIGNALING TRIGGERS TUMOR-PROMOTING INFLAMMATION THAT CAN BE TARGETED TO THERAPY

摘要

TNFR2-expressing neuroblastoma cells activate monocytes via contact-dependent mTNFα signaling, leading to production of sTNFα and IL-6 by monocytes that in turn bind to TNFR1 and IL-6R on neuroblastoma cells and stimulate tumor growth via activation of NF-κB and Sta3 signaling pathways. Growing tumor recruit additional monocytes resulting in a self-promoting inflammation that fuel tumor growth. TNF inhibitors can terminate this feed-forward signal amplification loop and inhibit tumor growth. Embodiments of the disclosure include a method of using TNF inhibitors for the treatment of neuroblastoma in a subject in need thereof. Also disclosed herein is a method of a method of using TNF inhibitors for reducing tumor-promoting inflammation in an individual with cancer.