Summary of project PR001662

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR001662. The data can be accessed directly via it's Project DOI: 10.21228/M8VX33 This work is supported by NIH grant, U2C- DK119886.


Project ID: PR001662
Project DOI:doi: 10.21228/M8VX33
Project Title:Hydroxyproline Modulates Adaptive PD-L1 Expression and Autophagy
Project Summary:The immune checkpoint protein PD-L1 plays critical roles in both immune system homeostasis and tumor progression. Impaired PD-1/PD-L1 function promotes autoimmunity and PD-L1 expression within tumors promotes immune evasion. If and how changes in metabolism or defined metabolites regulate PD-L1 expression is not fully understood. Here, using a metabolomics activity screening-based approach, we have determined that hydroxyproline (Hyp) significantly and directly enhances adaptive (i.e., IFN-γ induced) PD-L1 expression in multiple relevant myeloid and cancer cell types. Mechanistic studies reveal that Hyp acts as an inhibitor of IFN-γ-induced autophagic flux, which allows it to regulate this negative feedback mechanism, thereby contributing to its overall effect on PD-L1 expression. Due to its prevalence in fibrotic tumors, these findings suggest that hydroxyproline could contribute to the establishment of an immunosuppressive tumor microenvironment and that Hyp metabolism could be targeted to pharmacologically control PD-L1 expression for the treatment of cancer or autoimmune diseases.
Institute:Scripps Research Institute/University of California, Los Angeles
Last Name:Palermo
First Name:Amelia
Address:Los Angeles, CA, USA 90095

Summary of all studies in project PR001662

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST002577 Hydroxyproline Modulates Adaptive PD-L1 Expression and Autophagy Homo sapiens Scripps Research Institute/University of California, Los Angeles MS* 2023-05-17 1 60 Uploaded data (2.1G)*