PMID- 30253648
OWN - NLM
STAT- MEDLINE
DCOM- 20191101
LR  - 20191101
IS  - 1936-086X (Electronic)
IS  - 1936-0851 (Linking)
VI  - 12
IP  - 10
DP  - 2018 Oct 23
TI  - Local Blockade of Interleukin 10 and C-X-C Motif Chemokine Ligand 12 with 
      Nano-Delivery Promotes Antitumor Response in Murine Cancers.
PG  - 9830-9841
LID - 10.1021/acsnano.8b00967 [doi]
AB  - In many cancers, the tumor microenvironment (TME) is largely immune suppressive, 
      blocking the antitumor immunity and resulting in immunotherapy resistance. 
      Interleukin 10 (IL-10) is a major player controlling the immunosuppressive TME in 
      different murine tumor models. Increased IL-10 production suppresses intratumoral 
      dendritic cell production of interleukin 12, thereby limiting antitumor cytotoxic 
      T-cell responses and activation of NK cells during therapy. We engineered, 
      formulated, and delivered genes encoding an IL-10 protein trap to change 
      immunosuppressive TME, which could enhance antitumor immunity. Additionally, to 
      achieve stronger and long-term therapeutic efficacy in a pancreatic cancer model, 
      we targeted C-X-C motif chemokine ligand 12 (CXCL12), a key factor for inhibiting 
      T-cell tumor infiltration, and simultaneously delivered an IL-10 trap. Following 
      three injections of the lipid-protamine-DNA (LPD) nanoparticles loaded with trap 
      genes (IL-10 trap and CXCL12 trap), we found tumor growth reduction and 
      significantly prolonged survival of the host compared to control groups. 
      Furthermore, the combination trap gene treatment significantly reduced 
      immunosuppressive cells, such as M2 macrophages, MDSCs, and PD-L1(+) cells, and 
      activated immunosuppressive tolerogenic dendritic cells, NK cells, and 
      macrophages intratumorally. We have also shown that, when effectively delivered 
      to the tumor, the IL-10 trap gene alone can inhibit triple-negative breast cancer 
      growth. This strategy may allow clinicians and researchers to change the 
      immunosuppressive microenvironment in the tumor with either a single therapeutic 
      agent or in combination with other immunotherapies to prime the immune system, 
      preventing cancer invasion and prolonging patient survival.
FAU - Shen, Limei
AU  - Shen L
FAU - Li, Jingjing
AU  - Li J
FAU - Liu, Qi
AU  - Liu Q
FAU - Song, Wantong
AU  - Song W
FAU - Zhang, Xueqiong
AU  - Zhang X
FAU - Tiruthani, Karthik
AU  - Tiruthani K
FAU - Hu, Haiyang
AU  - Hu H
FAU - Das, Manisit
AU  - Das M
FAU - Goodwin, Tyler Jay
AU  - Goodwin TJ
FAU - Liu, Rihe
AU  - Liu R
FAU - Huang, Leaf
AU  - Huang L
AUID- ORCID: 0000-0002-9421-8283
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180928
PL  - United States
TA  - ACS Nano
JT  - ACS nano
JID - 101313589
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Cxcl12 protein, mouse)
RN  - 0 (IL10 protein, mouse)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Animals
MH  - Cell Proliferation
MH  - Chemokine CXCL12/genetics/*immunology
MH  - *Drug Delivery Systems
MH  - Female
MH  - HEK293 Cells
MH  - Humans
MH  - Interleukin-10/genetics/*immunology
MH  - Killer Cells, Natural/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Nanoparticles/chemistry
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Triple Negative Breast Neoplasms/immunology/*therapy
MH  - Tumor Cells, Cultured
MH  - Tumor Microenvironment/immunology
OTO - NOTNLM
OT  - C-X-C motif chemokine ligand 12
OT  - interleukin 10
OT  - nanoparticle
OT  - pancreatic ductal adenocarcinoma
OT  - triple-negative breast cancer
EDAT- 2018/09/27 06:00
MHDA- 2019/11/02 06:00
CRDT- 2018/09/27 06:00
PHST- 2018/09/27 06:00 [pubmed]
PHST- 2019/11/02 06:00 [medline]
PHST- 2018/09/27 06:00 [entrez]
AID - 10.1021/acsnano.8b00967 [doi]
PST - ppublish
SO  - ACS Nano. 2018 Oct 23;12(10):9830-9841. doi: 10.1021/acsnano.8b00967. Epub 2018 
      Sep 28.