Targeting the Innate Immune Kinase IRAK1 in Radioresistant Cancer: Double-Edged Sword or One-Two Punch?

ABSTRACT: Antitumor immunity has emerged as a favorable byproduct of radiation therapy (RT), whereby tumor-associated antigens released from irradiated cells unleash innate and adaptive attacks on tumors located both within and outside the radiation field. RT-induced immune responses further provide actionable targets for overcoming tumor resistance to RT (R-RT); immunotherapy (IT) with checkpoint inhibitors or Toll-like receptor (TLR) agonists can markedly improve, if not synergize with, RT in preclinical models, and several of these drugs are currently investigated as radiosensitizers in patients. In an unbiased chemical-genetic screen in a zebrafish model of tumor R-RT, we unexpectedly found that Interleukin 1 Receptor-Associated Kinase 1 (IRAK1), a core effector of TLR-mediated innate immunity,

SUBMITTER: Liu PH 

PROVIDER: S-EPMC6866135 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature