Interleukin-15 and cancer: some solved and many unsolved questions.

Journal for Immunotherapy of Cancer
Piera Filomena FioreBruno Azzarone

Abstract

Soluble interleukin (IL)-15 exists under two forms: as monomer (sIL-15) or as heterodimeric complex in association with sIL-15Rα (sIL-15/IL-15Rα). Both forms have been successfully tested in experimental tumor murine models and are currently undergoing investigation in phase I/II clinical trials. Despite more than 20 years research on IL-15, some controversial issues remain to be addressed. A first point concerns the detection of the sIL-15/IL-15Rα in plasma of healthy donors or patients with cancer and its biological significance. The second and third unsolved question regards the protumorigenic role of the IL-15/IL-15Rα complex in human cancer and the detrimental immunological consequences associated to prolonged exposure of natural killer (NK) cells to both forms of soluble IL-15, respectively. Data suggest that in vivo prolonged or repeated exposure to monomeric sIL-15 or the soluble complex may lead to NK hypo-responsiveness through the expansion of the CD8+/CD44+ T cell subset that would suppress NK cell functions. In vitro experiments indicate that soluble complex and monomeric IL-15 may cause NK hyporesponsiveness through a direct effect caused by their prolonged stimulation, suggesting that this mechanism could also be...Continue Reading

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Methods Mentioned

BETA
ELISA
biopsies
transgenic

Clinical Trials Mentioned

NCT02395822
NCT01385423
NCT03388632
NCT01572493
NCT01021059
NCT01369888
NCT01875601
NCT01727076
NCT01885897
NCT02523469

Software Mentioned

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