ABSTRACT
Stenotrophomonas maltophilia is an opportunistic pathogen exhibiting resistance to multiple antimicrobials. This study reports the complete genome of an S. maltophilia siphophage, Summit. Its genome of 95,728 bp has 148 protein-coding genes and 5 tRNAs, including 1 predicted suppressor tRNA. Possible target genes for the suppressor tRNA are not identified.
ABSTRACT
Streptomyces sp. strain Mg1 is a competitive soil-dwelling bacterium that secretes antibiotics that inhibit growth of Bacillus subtilis Here, we present the genome sequence of Sycamore, a 44,694-bp Streptomyces sp. Mg1 siphophage with 66 predicted protein-coding genes, that is similar to phage genome sequences in the Lomovskayavirus genus.
ABSTRACT
PD-L1 is expressed in tumor cells and its interaction with PD-1 plays an important role in evading immune surveillance; this can be overcome using PD-L1 or PD-1 immunotherapy antibodies. This study reports a novel approach for targeting PD-L1. In human breast cancer cell lines and 4T1 mouse mammary tumor cells, PD-L1 expression was regulated by the nuclear receptor NR4A1/Sp1 complex bound to the proximal germinal center (GC)-rich region of the PD-L1 gene promoter. Treatment of breast cancer cells with bis-indole-derived NR4A1 antagonists including 1,1-bis(3'-indolyl)-1-(3-chloro-4-hydroxy-5-methoxyphenyl)methane (Cl-OCH3) decreased expression of PD-L1 mRNA, promoter-dependent luciferase activity, and protein. In in vivo studies using a syngeneic mouse model bearing orthotopically injected 4T1 cells, Cl-OCH3 decreased tumor growth and weight and inhibited lung metastasis. Cl-OCH3 also decreased expression of CD3+/CD4+/CD25+/FoxP3+ regulatory T cells and increased the Teff/Treg ratio. Therefore, the potent anticancer activities of NR4A1 antagonists are also accompanied by enhanced antitumor immunity in PD-L1-expressing triple-negative breast cancer and thus represent a novel class of drugs that mimic immunotherapy. SIGNIFICANCE: These findings show that the orphan nuclear receptor NR4A1 controls PD-L1 expression and identify a chemical probe capable of disrupting this regulatory axis.
