PMID- 38319978
OWN - NLM
STAT- Publisher
LR  - 20240206
IS  - 1936-086X (Electronic)
IS  - 1936-0851 (Linking)
DP  - 2024 Feb 6
TI  - Delivery of Interferon beta-Encoding Plasmid via Lipid Nanoparticle Restores 
      Interferon beta Expression to Enhance Antitumor Immunity in Colon Cancer.
LID - 10.1021/acsnano.3c10972 [doi]
AB  - Type I interferon (IFN-I) plays a critical role in host cancer 
      immunosurveillance, but its expression is often impaired in the tumor 
      microenvironment. We aimed at testing the hypothesis that cationic lipid 
      nanoparticle delivery of interferon beta (IFNbeta)-encoding plasmid to tumors is 
      effective in restoring IFNbeta expression to suppress tumor immune evasion. We 
      determined that IFN-I function in tumor suppression depends on the host immune 
      cells. IFN-I activates the expression of Cxcl9 and Cxcl10 to enhance T cell tumor 
      infiltration. RNA-Seq detected a low level of IFNalpha13 and IFNbeta in colon tumor 
      tissue. scRNA-Seq revealed that IFNbeta is expressed in immune cell subsets in 
      non-neoplastic human tissues and to a lesser degree in human colon tumor tissues. 
      Forced expression of IFNalpha13 and IFNbeta in colon tumor cells up-regulates major 
      histocompatibility complex I (MHC I) expression and suppresses colon tumor growth 
      in vivo. In human cancer patients, IFNbeta expression is positively correlated with 
      human leukocyte antigen (HLA) expression, and IFN-I signaling activation 
      correlates with the patient response to PD-1 blockade immunotherapy. To translate 
      this finding to colon cancer immunotherapy, we formulated a 
      1,2-dioleoyl-3-trimethylammonium propane (DOTAP)-cholesterol-encapsulated 
      IFNbeta-encoding plasmid (IFNBCOL01). IFNBCOL01 transfects colon tumor cells to 
      express IFNbeta to increase the level of MHC I expression. IFNBCOL01 therapy 
      transfects tumor cells and tumor-infiltrating immune cells to produce IFNbeta to 
      activate MHC I and granzyme B expression and inhibits colon tumor growth in mice. 
      Our data determine that lipid nanoparticle delivery of IFNbeta-encoding plasmid DNA 
      enhances tumor immunogenicity and T cell effector function to suppress colon 
      tumor growth in vivo.
FAU - Yang, Yingcui
AU  - Yang Y
AD  - School of Life Sciences, Tianjin University, Tianjin 300072, China.
FAU - Bo, Shixuan
AU  - Bo S
AD  - School of Life Sciences, Tianjin University, Tianjin 300072, China.
FAU - Liang, Liyan
AU  - Liang L
AD  - School of Life Sciences, Tianjin University, Tianjin 300072, China.
FAU - Deng, Kaidi
AU  - Deng K
AD  - School of Life Sciences, Tianjin University, Tianjin 300072, China.
FAU - Bai, Liya
AU  - Bai L
AD  - School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
FAU - Wang, Tao
AU  - Wang T
AD  - School of Life Sciences, Tianjin University, Tianjin 300072, China.
FAU - Wang, Yinsong
AU  - Wang Y
AUID- ORCID: 0000-0002-1403-2113
AD  - School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
FAU - Liu, Kebin
AU  - Liu K
AUID- ORCID: 0000-0003-1965-7240
AD  - Department of Biochemistry and Molecular Biology, Medical College of Georgia, 
      Augusta, Georgia 30912, United States.
AD  - Georgia Cancer Center, Augusta, Georgia 30912, United States.
FAU - Lu, Chunwan
AU  - Lu C
AUID- ORCID: 0000-0002-3823-9434
AD  - School of Life Sciences, Tianjin University, Tianjin 300072, China.
LA  - eng
PT  - Journal Article
DEP - 20240206
PL  - United States
TA  - ACS Nano
JT  - ACS nano
JID - 101313589
SB  - IM
OTO - NOTNLM
OT  - Cationic lipid-DNA nanoparticle
OT  - DOTAP-cholesterol
OT  - Immune suppression
OT  - Immunogenicity
OT  - Lipid nanoparticle gene therapy
OT  - Type I IFN
EDAT- 2024/02/06 18:42
MHDA- 2024/02/06 18:42
CRDT- 2024/02/06 13:43
PHST- 2024/02/06 18:42 [medline]
PHST- 2024/02/06 18:42 [pubmed]
PHST- 2024/02/06 13:43 [entrez]
AID - 10.1021/acsnano.3c10972 [doi]
PST - aheadofprint
SO  - ACS Nano. 2024 Feb 6. doi: 10.1021/acsnano.3c10972.