Stat3 as a potential target for cancer immunotherapy.
The abilities of tumor cells to proliferate uncontrollably, resist apoptosis, induce vasculature formation, and invade distant organs are well-recognized hallmarks of cancer. More recently, the capability of tumors to evade immune surveillance and avoid destruction by the immune system has also gained significant acceptance in the cancer research field. However, the initial explanation for the lack of antitumor immune responses was ascribed to mutations affecting tumor-associated antigen expression, antigen processing, and presentation. Although these mutations undoubtedly facilitate tumor immune evasion, they cannot account for how tumors remain undetected before the occurrence of these genetic alterations. Moreover, the tumor microenvironment, whose pivotal role in immune paralysis is gaining appreciation, does not seem to directly cause these mutations. In addition, many tumors retain intact genes encoding major histocompatibility complex, costimulatory molecules and tumor antigens, but with reduced expression levels in the presence of tumor-secreted factors. Discoveries from several recent studies support the hypothesis that oncogenesis itself, as a result of overactivity of growth factor receptors, cytokine receptors, or oncoproteins, coordinates immune evasion. In particular, signal transducer and transcription activator 3 (Stat3), which is a point of convergence for many oncogenic pathways, has emerged as a critical mediator of tumor immune evasion at multiple levels. As a result, molecules involved in the oncogenic signaling pathways, particularly Stat3, provide targets for cancer immunotherapy.
Kortylewski
Marcin
M
Division of Cancer Immunotherapeutics and Tumor Immunology, The Beckman Research Institute of City of Hope National Medical Center, Duarte, CA 91010, USA.
Yu
Hua
H
D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D016207:Cytokines; D050796:STAT3 Transcription Factor