Etection of tumor cell growth inhibition. Thereafter, macrophagesTaBle 1 Literature on induction of macrophage tumoricidal activity by TLR agonists. Tlr agonist Lipopolysaccharide (LPS), lipid A (TLR4), RNA, and poly(I:C) (TLR3) LPS LPS Lipotechoic acid (LTA) (TLR2/6), SP-96 Epigenetic Reader Domain lipomannan (TLR2) LPS, CpG (TLR9) Functional assay made use of GI by manual counting of cells effector cells PM from DBA/2 or CBA mice PM from C3H/HeN, C3H/HeJ mice Human macrophages from PBMCs Bone marrow derived macrophages from DA rats PM from C3h/HeJ, CB17 SCID/beige or C57BL/6 mice PM from C3H/HeN mice PM from C57BL/6 mice Target cells L5178Y conclusion All agents Sulfentrazone Inhibitor induced tumoricidal activity in macrophages LPS induced tumoricidal activity, and MAF acted synergistically LPS induce tumoricidal activity, and MAF acted synergistically Some LTAs induced powerful tumoricidal activity, other LTAs and lipomannan significantly less ref (17)GI by cell quantity, cell death by release of thymidine Cell death by thymidine labeling Cell death by release of thymidine GI by thymidine labeling and cell death by flow cytometry Cell death by chrome release assay GI by thymidine labeling and cell death by flow cytometry Cell death by chrome release assay GI by thymidine labeling3T12 SK-BR-3 and HT-29 P-815 and DA tumor cells(20) (44) (34) (45)L5178Y, B16, RENCA, CpG and LPS combined or either M21, NXS2, OVCAR issue combined with in vivo anti-CD40 ligation induced tumoricidal activity MBT-2 B16, L5178Y and NXS2 3LL Lewis Both LPS and BCG induced tumoricidal activity In vivo stimulation with CpG induced tumoricidal activity in vitro, which was improved by adding LPS In vivo poly(I:C) induced in vitro tumoricidal activity LPS synergized with in vivo stimulation with anti-CD40 and CpG to induce in vitro tumoricidal activity TGF- inhibition combined with TLR4 or TLR7 ligation induced tumoricidal activity R848 induced tumoricidal activity, but not PamLPS, BCG LPS, CpG(46) (47)Poly(I:C)Tumor-associated macrophages (TAMs) from C57BL/6 mice PM from C57BL/6 mice(33)LPS, CpGB(48)LPS, gardiquimod (TLR7)Cell death by assay for luciferaseCD11b+ CD11c- TAMs from C57/BL6 mice mMDCs from human PBMCsMN/MCA(35)R848 (TLR7/8), Pam3 TLR(1/2)Cell death by flow cytometryA(36)GI, growth inhibition; PM, peritoneal macrophages; ds, double stranded; MAF, macrophage-activating issue (interferon-); PBMCs, peripheral blood mononuclear cells; BCG, Bacillus Calmette u in; TGF-, tumor necrosis issue beta; iNOS, inducible nitric oxide synthase; mMDCs, monocytic myeloid-derived suppressor cells.Frontiers in Immunology www.frontiersin.orgOctober 2017 Volume 8 ArticleM ler et al.Induction of M1 Antitumor MacrophagesFigUre 1 Lipopolysaccharide (LPS) and IFN- synergize to induce tumoricidal activity in macrophages. (a) Time-line for the growth inhibition assay used for measuring macrophage cytotoxic and cytostatic activity toward tumor cells. (B) Mitomycin C-treated bone marrow derived macrophages (BMDMs) have been stimulated for 24 h with many LPS concentrations prior to addition of five,000 MOPC315 tumor cells/well, resulting in the indicated macrophage to target cell ratios. The development with the tumor cells was quantified by measuring incorporation of radiolabeled thymidine and is shown on the y-axis as imply counts per minute (cpm) values of triplicates ?SD. The 3 columns towards the left show proliferation of BMDMs alone (tumor cells had been not added). (c) BMDMs had been stimulated with IFN- (40 ng/ml) in combination with distinct concentrations of LPS.
Posted inUncategorized