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Dr. Christina Sternberg
MedUni Wien RESEARCHER OF THE MONTH July 2025
Prostate cancer is the second most common cancer in men worldwide. While IL6ST-mediated signaling and aberrant STAT3 activation have been implicated in various cancers, their specific roles in prostate cancer remains unclear. In this study, we induced IL6ST activation in the prostate epithelium of a prostate cancer mouse model and analyzed IL6ST expression in large patient cohorts. Our results show that IL6ST activation promotes STAT3 signaling, leading to reduced tumor growth by inducing senescence via the STAT3/ARF/p53 pathway and by enhancing cytotoxic T-cell recruitment in our mouse model. In patients, high IL6ST mRNA levels were associated with improved recurrence-free survival, increased expression of senescence markers and a shift toward an immune-hot tumor microenvironment. These findings highlight a context-dependent, tumor-suppressive role of IL6ST/STAT3 signaling in prostate cancer and suggest IL6ST activation, rather than inhibition, as a potential therapeutic approach.
Selected Literature
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Sternberg C, Raigel M, Limberger T, et al (2024) Cell-autonomous IL6ST activation suppresses prostate cancer development via STAT3/ARF/p53-driven senescence and confers an immune-active tumor microenvironment. Mol Cancer 23:245
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Schaper F, Rose-John S (2015) Interleukin-6: Biology, signaling and strategies of blockade. Cytokine Growth Factor Rev 26:475–487
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Huang W, Hickson LTJ, Eirin A, Kirkland JL, Lerman LO (2022) Cellular senescence: the good, the bad and the unknown. Nat Rev Nephrol 18:611–627
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Stultz J, Fong L (2021) How to turn up the heat on the cold immune microenvironment of metastatic prostate cancer. Prostate Cancer Prostatic Dis 24:697–717