BTN1A1 is a novel immune checkpoint mutually exclusive to PD-L1.

Background: While Programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) blockade is a potent antitumor treatment strategy, it is effective in only limited subsets of patients with cancer, emphasizing the need for the identification of additional immune checkpoints. Butyrophilin 1A1 (BTN1A1) has been reported to exhibit potential immunoregulatory activity, but its ability to function as an immune checkpoint remains to be systematically assessed, and the mechanisms underlying such activity have yet to be characterized.

Methods: BTN1A1 expression was evaluated in primary tumor tissue samples, and its ability to suppress T-cell activation and T cell-dependent tumor clearance was examined.

DNA binding site kinetics of a large antiviral polyamide.

Polyamides (PAs) are powerful DNA ligands that can bind the minor groove of DNA with high affinity and specificity. While the characterization of PA-DNA behavior has focused principally on hairpin PAs 6-8 rings in size, there is increasing evidence that their behavior does not necessarily reflect the complexities that are emerging from studies of larger hairpin PAs, particularly concerning sequence mismatch tolerance and observed but unaddressed high PA-target site binding stoichiometries. To explore these complexities in more detail, kinetics studies of binding a large anti-HPV hairpin polyamide to an isolated DNA recognition site are described.

Targeting Glycosylated PD-1 Induces Potent Antitumor Immunity.

Immunotherapies targeting programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) immune checkpoints represent a major breakthrough in cancer treatment. PD-1 is an inhibitory receptor expressed on the surface of activated T cells that dampens T-cell receptor (TCR)/CD28 signaling by engaging with its ligand PD-L1 expressed on cancer cells. Despite the clinical success of PD-1 blockade using mAbs, most patients do not respond to the treatment, and the underlying regulatory mechanisms of PD-1 remain incompletely defined.

DNA binding thermodynamics and site stoichiometry as a function of polyamide size.

The interactions of 6-8 ring hairpin polyamides (PAs) with the minor groove of DNA have been investigated extensively. More recent studies of large antiviral PAs (14-20 rings) active against small DNA tumor viruses lead to questions regarding the extent to which the DNA binding behaviors of the well studied, smaller PAs can be reliably extrapolated to the larger ones. Described here is the first reported study of hairpin PA-DNA binding thermodynamics as a function of PA size (6-20 rings).

Eradication of Triple-Negative Breast Cancer Cells by Targeting Glycosylated PD-L1.

Protein glycosylation provides proteomic diversity in regulating protein localization, stability, and activity; it remains largely unknown whether the sugar moiety contributes to immunosuppression. In the study of immune receptor glycosylation, we showed that EGF induces programmed death ligand 1 (PD-L1) and receptor programmed cell death protein 1 (PD-1) interaction, requiring β-1,3-N-acetylglucosaminyl transferase (B3GNT3) expression in triple-negative breast cancer. Downregulation of B3GNT3 enhances cytotoxic T cell-mediated anti-tumor immunity.

ANAC012, a member of the plant-specific NAC transcription factor family, negatively regulates xylary fiber development in Arabidopsis thaliana.

Vascular plants evolved to have xylem that provides physical support for their growing body and serves as a conduit for water and nutrient transport. In a previous study, we used comparative-transcriptome analyses to select a group of genes that were upregulated in xylem of Arabidopsis plants undergoing secondary growth. Subsequent analyses identified a plant-specific NAC-domain transcription factor gene (ANAC012) as a candidate for genetic regulation of xylem formation.