Deletion of Monoamine Oxidase A in a Prostate Cancer Model Enhances Anti-tumor Immunity Through Reduced Immune Suppression

Jessica A Lapierre, Lauren A Geary, Julie K Jang, Alan L Epstein, Frank Hong, Jean C Shih
We have previously shown that monoamine oxidase A (MAO A) mediates prostate growth and metastasis.  Further, MAO A/Pten double knockout (DKO) mice were generated and demonstrated that the deletion of MAO A delayed prostate tumor development in the Pten knockout mouse model of prostate adenocarcinoma.  Here, we investigated its effect on immune cells in the tumor microenvironment in MAO A/Pten DKO mouse model.  Our results shows that Paraffin embedded prostate tissues from MAO A/Pten DKO mice had elevated markers of immune stimulation (CD8+ cytotoxic T cells, granzyme B, and IFNγ) and decreased expression of markers of immune suppression (FoxP3, CD11b, HIF-1-alpha, and arginase 1) compared to parental Pten knockouts (MAO A wildtype). CD11b+ myeloid derived suppressor cells (MDSC) were the primary immunosuppressive cell types in these tumors. The data suggest that deletion of MAO A reduces immune suppression in prostate tumors to enhance antitumor immunity in prostate .  Thus, MAO A inhibitor may alleviate immune suppression, increase the antitumor immune response and be used for immunotherapy. 

DOI: 10.1016/j.bbrc.2022.10.016