Immunosuppression articles from across Nature Portfolio

Prostaglandin E2 from the tumour microenvironment impairs interleukin-2 sensing by tumour-infiltrating lymphocytes, restricting proliferative response and promoting T cell death via metabolic impairment and ferroptosis. 

Xenotransplantation is an imminent clinical reality but concerns remain around the logistics of procurement and the experimental immunosuppression regimens required to achieve long-term xenograft survival. Here the authors show more than 6 month survival of genetically modified porcine kidneys in baboons after regulatory compliant organ procurements, clinically relevant organ preservation times and FDA-approved immunosuppressive reagents.

Graft-versus-Host disease is a major complication after allogeneic bone marrow transplantation and is ameliorated by adoptively transferred donor regulatory T cells. Here, the authors apply transcriptomic and TCR profiling to assess regulatory T cell organ-specific adaptation in murine bone marrow transplantation models.

Antigen-specific immunosuppression can be enhanced by genetically modifying mesenchymal stromal cells with chimaeric antigen receptors, as shown for the treatment of graft-versus-host disease in mice.

Fusing the anti-inflammatory enzyme indoleamine 2,3-dioxygenase to the tissue-anchoring protein galectin-3 ameliorates inflammation at the injection site while avoiding systemic immune suppression, as shown in multiple rodent models of inflammation.

Modulation of T cell immune checkpoints combined with inhibition of chemokine receptors on myeloid-derived suppressor cells can reprogram the highly suppressive tumor immune microenvironment of pancreatic ductal adenocarcinoma (PDAC), and generates durable complete responses in a PDAC mouse model. These results provide a testable clinical regimen for human PDAC.

The response of circulating effector CD4 T cells to type I interferons (IFN-I) correlates with the overall survival of patients with cancer receiving immune checkpoint inhibition. IFN-I responsiveness is already epigenetically encoded before treatment initiation, highlighting a deterministic, clinically relevant feature that can predict therapeutic efficacy.