title: Empty liposomes induce antitumoral effects associated with macrophage responses distinct from those of the TLR1/2 agonist Pam3CSK 4 (BLP).
abstract: Liposomes are frequently used in cancer therapy to encapsulate and apply anticancer drugs. Here, we show that a systemic treatment of mice bearing skin tumors with empty phosphatidylcholine liposomes (PCL) resulted in inhibition of tumor growth, which was similar to that observed with the synthetic bacterial lipoprotein and TLR1/2 agonist Pam(3)CSK(4) (BLP). Both compounds led to a substantial decrease of macrophages in spleen and in the tumor-bearing skin. Furthermore, both treatments induced the expression of typical macrophage markers in the tumor-bearing tissue. As expected, BLP induced the expression of the M1 marker genes Cxcl10 and iNOS, whereas PCL, besides inducing iNOS, also increased the M2 marker genes Arg1 and Trem2. In vitro experiments demonstrated that neither PCL nor BLP influenced proliferation or survival of tumor cells, whereas both compounds inhibited proliferation and survival and increased the migratory capacity of bone marrow-derived macrophages (BMDM). However, in contrast to BLP, PCL did not activate cytokine secretion and induced a different BMDM phenotype. Together, the data suggest that similar to BLP, PCL induce an antitumor response by influencing the tumor microenvironment, in particular by functional alterations of macrophages, however, in a distinct manner from those induced by BLP.
authors.affiliation: Institute of Human Genetics, University Medical Center, Heinrich-Düker-Weg 12, 37073, Göttingen, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: König
authors.forename: Tommy
authors.initials: T
authors.lastname: Regen
authors.forename: Kai
authors.initials: K
authors.lastname: Dittmann
authors.forename: Michael
authors.initials: M
authors.lastname: Engelke
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wienands
authors.forename: Reto
authors.initials: R
authors.lastname: Schwendener
authors.forename: Uwe-Karsten
authors.initials: UK
authors.lastname: Hanisch
authors.forename: Tobias
authors.initials: T
authors.lastname: Pukrop
authors.forename: Heidi
authors.initials: H
authors.lastname: Hahn
mesh_terms: D000818:Animals; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D055666:Lipopeptides / Q000494:pharmacology*; D008081:Liposomes / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D011897:Random Allocation; D051194:Toll-Like Receptor 1 / Q000819:agonists* / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists* / Q000276:immunology / Q000378:metabolism
chemical_list: D055666:Lipopeptides; D008081:Liposomes; C508075:Pam(3)CSK(4) peptide; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2
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