Bile acid synthesis impedes tumor-specific T cell responses during liver cancer.

The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid-CoA:amino acid -acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy.

[Delphi-Study: Evaluation of the new job profile "Chief Digital Officer" in German hospitals].

Introduction: The main objective of the present study was to analyze the new job profile "Chief Digital Officer (CDO) in German hospitals". Here, best practices for the introduction of the job profile should be determined and the need for a CDO position to execute the digital transformation should be evaluated.

Methods: A standardized three-stage online Delphi process (expert consensus finding) followed by a roundtable discussion was performed, including 16 experts.

Spatial proteomics reveals sirtuin 1 to be a determinant of T-cell infiltration in human melanoma.

Background: The tumour microenvironment significantly influences the clinical response of patients to therapeutic immune checkpoint inhibition (ICI), but a comprehensive understanding of the underlying immune-regulatory proteome is still lacking.

Objectives: To decipher targetable biologic processes that determine tumour-infiltrating lymphocytes (TiLs) as a cellular equivalent of clinical response to ICI.

Methods: We mapped the spatial distribution of proteins in TiL-enriched vs.

Provision of hospice and palliative care and implementation of advance care planning for residents in German nursing homes - a cross-sectional study.

Background: Demographic changes are leading to a rise in the demand for care services, with nursing homes (NHs) playing an increasingly important role in end-of-life care. Evidence suggests that NH residents at the end of life significantly benefit from hospice and palliative care and the implementation of advance care planning (ACP). In 2018, Germany passed a law to promote the implementation of ACP in NHs and to enable the refinancing of ACP services by the statutory health insurance funds.

Nutrient-driven histone code determines exhausted CD8 T cell fates.

Exhausted T cells (TEX) in cancer and chronic viral infections undergo metabolic and epigenetic remodeling, impairing their protective capabilities. However, the impact of nutrient metabolism on epigenetic modifications that control TEX differentiation remains unclear. We showed that TEX cells shifted from acetate to citrate metabolism by downregulating acetyl-CoA synthetase 2 (ACSS2) while maintaining ATP-citrate lyase (ACLY) activity.