PMID- 31700995
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231014
IS  - 2374-4677 (Print)
IS  - 2374-4677 (Electronic)
IS  - 2374-4677 (Linking)
VI  - 5
DP  - 2019
TI  - Retinoid X receptor agonist LG100268 modulates the immune microenvironment in 
      preclinical breast cancer models.
PG  - 39
LID - 10.1038/s41523-019-0135-5 [doi]
LID - 39
AB  - Despite numerous therapeutic advances in the past decade, breast cancer is 
      expected to cause over 42,000 deaths in the United States in 2019. Breast cancer 
      had been considered an immunologically silent tumor; however recent findings 
      suggest that immune cells play important roles in tumor growth even in the 
      breast. Retinoid X receptors (RXRs) are a subclass of nuclear receptors that act 
      as ligand-dependent transcription factors that regulate a variety of cellular 
      processes including proliferation and differentiation; in addition, they are 
      essential for macrophage biology. Rexinoids are synthetic molecules that bind and 
      activate RXRs. Bexarotene is the only rexinoid approved by the FDA for the 
      treatment of refractory cutaneous T-cell lymphoma. Other more-potent rexinoids 
      have been synthesized, such as LG100268 (LG268). Here, we report that treatment 
      with LG 268, but not bexarotene, decreased infiltration of myeloid-derived 
      suppressor cells and CD206-expressing macrophages, increased the expression of 
      PD-L1 by 50%, and increased the ratio of CD8/CD4, CD25 T cells, which correlates 
      with increased cytotoxic activity of CD8 T cells in tumors of MMTV-Neu mice (a 
      model of HER2-positive breast cancer). In the MMTV-PyMT murine model of triple 
      negative breast cancer, LG268 treatment of established tumors prolonged survival, 
      and in combination with anti-PD-L1 antibodies, significantly (p = 0.05) increased 
      the infiltration of cytotoxic CD8 T cells and apoptosis. Collectively, these data 
      suggest that the use of LG268, a RXR agonist, can improve response to immune 
      checkpoint blockade in HER2+ or triple-negative breast cancer.
CI  - (c) The Author(s) 2019.
FAU - Leal, Ana S
AU  - Leal AS
AD  - 1Department of Pharmacology & Toxicology, Michigan State University, East 
      Lansing, MI USA. ISNI: 0000 0001 2150 1785. GRID: grid.17088.36
FAU - Zydeck, Kayla
AU  - Zydeck K
AD  - 1Department of Pharmacology & Toxicology, Michigan State University, East 
      Lansing, MI USA. ISNI: 0000 0001 2150 1785. GRID: grid.17088.36
FAU - Carapellucci, Sarah
AU  - Carapellucci S
AD  - 1Department of Pharmacology & Toxicology, Michigan State University, East 
      Lansing, MI USA. ISNI: 0000 0001 2150 1785. GRID: grid.17088.36
FAU - Reich, Lyndsey A
AU  - Reich LA
AD  - 1Department of Pharmacology & Toxicology, Michigan State University, East 
      Lansing, MI USA. ISNI: 0000 0001 2150 1785. GRID: grid.17088.36
FAU - Zhang, Di
AU  - Zhang D
AD  - 1Department of Pharmacology & Toxicology, Michigan State University, East 
      Lansing, MI USA. ISNI: 0000 0001 2150 1785. GRID: grid.17088.36
FAU - Moerland, Jessica A
AU  - Moerland JA
AD  - 1Department of Pharmacology & Toxicology, Michigan State University, East 
      Lansing, MI USA. ISNI: 0000 0001 2150 1785. GRID: grid.17088.36
FAU - Sporn, Michael B
AU  - Sporn MB
AD  - 2Department of Molecular and Systems Biology, Dartmouth/Geisel School of Medicine 
      at Dartmouth, Hanover, NH USA. ISNI: 0000 0001 2179 2404. GRID: grid.254880.3
FAU - Liby, Karen T
AU  - Liby KT
AD  - 1Department of Pharmacology & Toxicology, Michigan State University, East 
      Lansing, MI USA. ISNI: 0000 0001 2150 1785. GRID: grid.17088.36
LA  - eng
GR  - T32 GM092715/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20191101
PL  - United States
TA  - NPJ Breast Cancer
JT  - NPJ breast cancer
JID - 101674891
PMC - PMC6825145
OTO - NOTNLM
OT  - Breast cancer
OT  - Cancer microenvironment
OT  - Pharmaceutics
OT  - Tumour immunology
COIS- Competing interestsThe authors declare no competing interests.
EDAT- 2019/11/09 06:00
MHDA- 2019/11/09 06:01
PMCR- 2019/11/01
CRDT- 2019/11/09 06:00
PHST- 2019/03/26 00:00 [received]
PHST- 2019/10/10 00:00 [accepted]
PHST- 2019/11/09 06:00 [entrez]
PHST- 2019/11/09 06:00 [pubmed]
PHST- 2019/11/09 06:01 [medline]
PHST- 2019/11/01 00:00 [pmc-release]
AID - 135 [pii]
AID - 10.1038/s41523-019-0135-5 [doi]
PST - epublish
SO  - NPJ Breast Cancer. 2019 Nov 1;5:39. doi: 10.1038/s41523-019-0135-5. eCollection 
      2019.