STAT3 inhibition for cancer therapy: Cell-autonomous effects only?

作者: Guido Kroemer , Lorenzo Galluzzi , Laurence Zitvogel

DOI: 10.1080/2162402X.2015.1126063

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摘要: A paper recently published in Science Translational Medicine describes a next-generation antisense oligonucleotide that specifically downregulates the expression of human signal transducer and activator transcription 3 (STAT3). Such an oligonucleotide, AZD9150, exerts antineoplastic effects on selected panel STAT3-dependent cancer cells growing vitro vivo (as xenografts immunodeficient mice). Moreover, preliminary data from Phase I clinical trial indicate AZD9150 may cause partial tumor regression patients with chemorefractory lymphoma non-small cell lung carcinoma. STAT3 not only participates cell-autonomous processes are required for survival growth malignant cells, but also limits their ability to elicit anticancer immune responses. contribute establishment immunosuppressive microenvironment. Thus, inhibition promote immunosurveillance by dual mechanism: (1) it increase immunogenicity via pathways; (2) favor reprogramming microenvironment toward immunostimulatory state. It will therefore be important explore whether immunological biomarkers predict efficacy clinic. This ameliorate patient stratification pave way rational combination therapies involving classical chemotherapeutics effects, immunotherapeutic agents such as checkpoint blockers.

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