Tumor infiltrating lymphocyes from Arid5a KO or WT murine tumors

From: Arid5a augments tryptophan metabolism and chemokine expression to promote the immune evasion of mesenchymal subtypes of pancreatic and colorectal cancer. The acquisition of mesenchymal traits leads to immune evasion in various cancers, but the molecular mechanisms that link tumor immune evasiveness and mesenchymal phenotypes remain unclear. We found that the expression levels of AT-rich interaction domain containing protein 5a (Arid5a), an RNA-binding protein, is substantially increased in mesenchymal tumor subtypes.
Conclusion:
The deletion of Arid5a in tumor cell lines enhanced antitumor immunity in immunocompetent mice but not in immunodeficient mice, highlighting the role of Arid5a in immune evasion. Furthermore, an Arid5a-deficient tumor microenvironment was shown to have robust antitumor immunity, as manifested by the suppressed infiltration of granulocytic myeloid-derived suppressor cells and regulatory T-cells, whereas infiltrated Tlymphocytes were more cytotoxic and less exhausted. Mechanistically, Arid5a stabilized Ido1 and Ccl2 mRNAs and augmented their expression, resulting in enhanced tryptophan catabolism and an immunosuppressive tumor microenvironment. Thus, our findings demonstrate the role of Arid5a beyond inflammatory diseases, and suggest Arid5a as a promising target for the treatment of immunotolerant malignant tumors.
Notes:
In these uploaded experiments the tumor infiltrating lymphocytes from murine Wildtype or Arid5a KO PDAC and MC38 tumors were assessed by mass cytometry. Samples uploaded are pregated Live_singlet_DNA+_debarcoded. Total CD45, CD4-Tcells and CD8 T-cells. Barcoding channels and channels not used for clustering were removed by Premessa panel editor. Raw ungated data is available on request.