Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Heterodimeric IL-15 (hetIL-15) reduces circulating tumor cells and metastasis formation improving chemotherapy and surgery in 4T1 mouse model of TNBC
Δημιουργός/Συγγραφέας:	Stravokefalou, Vasiliki [EL] Στέλλας, Δημήτρης[EN] Stellas, Dimitris Karaliota, Sevasti Nagy, Bethany A Valentin, Antonio Bergamaschi, Cristina Dimas, Konstantinos Pavlakis, George N
Ημερομηνία:	2022
Γλώσσα:	Αγγλικά
ISSN:	1664-3224
DOI:	10.3389/fimmu.2022.1014802
Άλλο:	36713398
Περίληψη:	Immunotherapy has emerged as a viable approach in cancer therapy, with cytokines being of great interest. Interleukin IL-15 (IL-15), a cytokine that supports cytotoxic immune cells, has been successfully tested as an anti-cancer and anti-metastatic agent, but combinations with conventional chemotherapy and surgery protocols have not been extensively studied. We have produced heterodimeric IL-15 (hetIL-15), which has shown anti-tumor efficacy in several murine cancer models and is being evaluated in clinical trials for metastatic cancers. In this study, we examined the therapeutic effects of hetIL-15 in combination with chemotherapy and surgery in the 4T1 mouse model of metastatic triple negative breast cancer (TNBC). hetIL-15 monotherapy exhibited potent anti-metastatic effects by diminishing the number of circulating tumor cells (CTCs) and by controlling tumor cells colonization of the lungs. hetIL-15 treatment in combination with doxorubicin resulted in enhanced anti-metastatic activity and extended animal survival. Systemic immune phenotype analysis showed that the chemoimmunotherapeutic regimen shifted the tumor-induced imbalance of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in favor of cytotoxic effector cells, by simultaneously decreasing PMN-MDSCs and increasing the frequency and activation of effector (CD8+T and NK) cells. Tumor resection supported by neoadjuvant and adjuvant administration of hetIL-15, either alone or in combination with doxorubicin, resulted in the cure of approximately half of the treated animals and the development of anti-4T1 tumor immunity. Our findings demonstrate a significant anti-metastatic potential of hetIL-15 in combination with chemotherapy and surgery and suggest exploring the use of this regimen for the treatment of TNBC.
Τίτλος πηγής δημοσίευσης:	Frontiers in immunology
Τόμος/Κεφάλαιο:	13
Θεματική Κατηγορία:	[EL] Ανοσολογία[EN] Immunology [EL] Θεραπευτική. Φαρμακολογία[EN] Therapeutics.Pharmacology [EL] Νεοπλάσματα. Όγκοι. Ογκολογία (περ. Καρκίνος, κακινογόνες ουσίες)[EN] Neoplasms. Tumors. Oncology (Incl.cancer, carcinogens) [EL] Βιοχημεία[EN] Biochemistry [EL] Κυτταρολογία[EN] Cytology
Λέξεις-Κλειδιά:	chemoimmunotherapy circulating tumor cells (CTCs) doxorubicin heterodimeric IL-15 (hetIL-15) metastasis surgery triple negative breast cancer (TNBC)
EU Grant identifier:	HHSN261201500003I
Κάτοχος πνευματικών δικαιωμάτων:	© 2023 Stravokefalou, Stellas, Karaliota, Nagy, Valentin, Bergamaschi, Dimas and Pavlakis.
Όροι και προϋποθέσεις δικαιωμάτων:	This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://doi.org/10.3389/fimmu.2022.1014802
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο