PMID- 30450098
OWN - NLM
STAT- MEDLINE
DCOM- 20191003
LR  - 20191007
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 9
DP  - 2018
TI  - Both Type I and Type II Interferons Can Activate Antitumor M1 Macrophages When 
      Combined With TLR Stimulation.
PG  - 2520
LID - 10.3389/fimmu.2018.02520 [doi]
LID - 2520
AB  - Triggering or enhancing antitumor activity of tumor-associated macrophages is an 
      attractive strategy for cancer treatment. We have previously shown that the 
      cytokine interferon-gamma (IFN-gamma), a type II IFN, could synergize with toll-like 
      receptor (TLR) agonists for induction of antitumor M1 macrophages. However, the 
      toxicity of IFN-gamma limits its clinical use. Here, we investigated whether the less 
      toxic type I IFNs, IFN-alpha, and IFN-beta, could potentially replace IFN-gamma for 
      induction of antitumor M1 macrophages. We measured in vitro the ability of type I 
      and II IFNs to synergize with TLR agonists for transcription of inducible nitric 
      oxide synthase (iNOS) mRNA and secretion of nitric oxide (NO) by mouse bone 
      marrow-derived macrophages (BMDMs). An in vitro growth inhibition assay was used 
      to measure both cytotoxic and cytostatic activity of activated macrophages 
      against Lewis lung carcinoma (LLC) cancer cells. We found that both type I and II 
      IFNs could synergize with TLR agonists in inducing macrophage-mediated inhibition 
      of cancer cell growth, which was dependent on NO. The ability of high dose 
      lipopolysaccharide (LPS) to induce tumoricidal activity in macrophages in the 
      absence of IFN-gamma was shown to depend on induction of autocrine type I IFNs. 
      Antitumor M1 macrophages could also be generated in the absence of IFN-gamma by a 
      combination of two TLR ligands when using the TLR3 agonist poly(I:C) which 
      induces autocrine type I IFNs. Finally, we show that encapsulation of poly(I:C) 
      into nanoparticles improved its potency to induce M1 macrophages up to 100-fold. 
      This study reveals the potential of type I IFNs for activation of antitumor 
      macrophages and indicates new avenues for cancer immunotherapy based on type I 
      IFN signaling, including combination of TLR agonists.
FAU - Muller, Elisabeth
AU  - Muller E
AD  - Tumor Immunology Lab, Department of Pathology, Rikshospitalet, Oslo University 
      Hospital, University of Oslo, Oslo, Norway.
AD  - Department of Biosciences, University of Oslo, Oslo, Norway.
FAU - Speth, Martin
AU  - Speth M
AD  - Department of Biosciences, University of Oslo, Oslo, Norway.
FAU - Christopoulos, Panagiotis F
AU  - Christopoulos PF
AD  - Tumor Immunology Lab, Department of Pathology, Rikshospitalet, Oslo University 
      Hospital, University of Oslo, Oslo, Norway.
FAU - Lunde, Anna
AU  - Lunde A
AD  - Tumor Immunology Lab, Department of Pathology, Rikshospitalet, Oslo University 
      Hospital, University of Oslo, Oslo, Norway.
FAU - Avdagic, Ajna
AU  - Avdagic A
AD  - Tumor Immunology Lab, Department of Pathology, Rikshospitalet, Oslo University 
      Hospital, University of Oslo, Oslo, Norway.
FAU - Oynebraten, Inger
AU  - Oynebraten I
AD  - Tumor Immunology Lab, Department of Pathology, Rikshospitalet, Oslo University 
      Hospital, University of Oslo, Oslo, Norway.
FAU - Corthay, Alexandre
AU  - Corthay A
AD  - Tumor Immunology Lab, Department of Pathology, Rikshospitalet, Oslo University 
      Hospital, University of Oslo, Oslo, Norway.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181102
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Interferon Type I)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Toll-Like Receptors)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Animals
MH  - Carcinoma, Lewis Lung/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects/physiology
MH  - Interferon Type I/*metabolism
MH  - Interferon-gamma/*metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophage Activation/drug effects/*physiology
MH  - Macrophages/drug effects/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Poly I-C/metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - Toll-Like Receptors/*metabolism
PMC - PMC6224375
OTO - NOTNLM
OT  - cancer
OT  - immunotherapy
OT  - interferon-alpha
OT  - interferon-beta
OT  - interferon-gamma
OT  - macrophages
OT  - nitric oxide
OT  - toll-like receptors
EDAT- 2018/11/20 06:00
MHDA- 2019/10/08 06:00
PMCR- 2018/01/01
CRDT- 2018/11/20 06:00
PHST- 2018/06/22 00:00 [received]
PHST- 2018/10/12 00:00 [accepted]
PHST- 2018/11/20 06:00 [entrez]
PHST- 2018/11/20 06:00 [pubmed]
PHST- 2019/10/08 06:00 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2018.02520 [doi]
PST - epublish
SO  - Front Immunol. 2018 Nov 2;9:2520. doi: 10.3389/fimmu.2018.02520. eCollection 
      2018.