New perspective on targeting the tumor suppressor p53 pathway in the tumor microenvironment to enhance the efficacy of immunotherapy.

摘要: About 50% of human cancers harbor somatic mutations the tumor suppressor p53 (p53 or Trp53) gene. Many those result in inactivation pathway and are often associated with stabilization accumulation mutant proteins. Therefore, increased expression tumors is frequently used as a surrogate marker for mutation inactivation. Moreover, this elevated also makes it an ideal antigen (TAA) cancer vaccines. Recent advances our understanding crucial transcription factor reveal that important sensor cellular stress under genotoxic, chemotoxic, pathological, even normal physiological conditions. Experimental clinical observations by laboratory others have demonstrated participates immune regulation dysfunction skews host responses towards pro-inflammation, which further promotes progression. Furthermore, recent studies using genetic approach revealed p53-restoration re-activation led to regression clearance, were at least partially caused activation innate antitumor immunity. Since many currently therapeutics, including radiotherapy chemotherapy, disrupt growth inducing DNA damage via genotoxic chemotoxic stress, activates microenvironment, we postulate some observed therapeutic benefits might be mediated through their stimulatory effects. Here, briefly review current potential molecular mechanisms and, subsequently, extend discussion immunostimulatory existing new approaches targeting p53-pathway alter immunological landscape maximizing immunotherapy outcome.