Please use this identifier to cite or link to this item: https://scidar.kg.ac.rs/handle/123456789/13877
Title: Dual blockage of PD-L/PD-1 and IL33/ST2 axes slows tumor growth and improves antitumor immunity by boosting NK cells
Authors: Jovanovic, Marina
Geller D.
Gajovic, Nevena
Jurisevic, Milena
Arsenijevic, Nebojsa
Jovanovic, Milan
Supic, Gordana
Vojvodic, Danilo
Jovanovic, Ivan
Issue Date: 2022
Abstract: Aims: Although separate blockage of either IL33/ST2 or PD-L/PD-1 axes has been shown to be beneficial in many tumors, co-blockage of IL33/ST2 and PD-L/PD-1 hasn't been studied yet. Main methods: 4T1 breast cancer and CT26 colon cancer were inducted in BALB/C wild type (WT) and BALB/C ST2 knockout mice, after which mice underwent anti PD-1 and anti IL-33 treatment. Key findings: Co-blockage of IL33/ST2 and PD-L/PD-1 delayed tumor appearance and slowed tumor growth. Enhanced NK cell cytotoxicity against 4T1 tumor cells in ST2 knockout anti-PD-1 treated mice was associated with overexpression of miRNA-150 and miRNA-155, upregulation of NFκB and STAT3, increased expression of activation markers and decreased expression of immunosuppressive markers in splenic and primary tumor derived NK cells. NK cells from ST2 knockout anti-PD-1 treated mice tend to proliferate more and are less prone to apoptosis. Accumulation of immunosuppressive myeloid derived suppressor cells and regulatory T cells was significantly impaired in spleen and primary tumor of ST2 knockout anti-PD-1 treated mice. Significance: Co-blockage of IL3/ST2 and PD-L/PD-1 axes impedes tumor progression more efficiently than single blockage of either axes, thus offering potential new approach to immunotherapy of tumors.
URI: https://scidar.kg.ac.rs/handle/123456789/13877
Type: article
DOI: 10.1016/j.lfs.2021.120214
ISSN: 0024-3205
SCOPUS: 2-s2.0-85121293917
Appears in Collections:Faculty of Medical Sciences, Kragujevac

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