The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity.

Immune checkpoint blockade is effective for some patients with cancer, but most are refractory to current immunotherapies and new approaches are needed to overcome resistance. The protein tyrosine phosphatases PTPN2 and PTPN1 are central regulators of inflammation, and their genetic deletion in either tumour cells or immune cells promotes anti-tumour immunity. However, phosphatases are challenging drug targets; in particular, the active site has been considered undruggable.

Epithelial HVEM maintains intraepithelial T cell survival and contributes to host protection.

Intraepithelial T cells (IETs) are in close contact with intestinal epithelial cells and the underlying basement membrane, and they detect invasive pathogens. How intestinal epithelial cells and basement membrane influence IET survival and function, at steady state or after infection, is unclear. The herpes virus entry mediator (HVEM), a member of the TNF receptor superfamily, is constitutively expressed by intestinal epithelial cells and is important for protection from pathogenic bacteria.

Physicians' challenges under El Salvador's criminal abortion prohibition.

El Salvador's criminal abortion law-one of the few in the world that prohibits all abortions and that is actively enforced against women-harms women's health and undermines the ethical duties of Salvadoran physicians and the standing of the medical profession. Under the criminal abortion regime, physicians are incentivized to disclose their patients' confidential medical information, in violation of their ethical duties, and public healthcare facilities have become sites of criminal investigation. These investigations target women not only for illegal abortions, but also for miscarriages and obstetric emergencies.