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

doi:10.1016/j.bbrc.2022.10.016

Deletion of monoamine oxidase A in a prostate cancer model enhances anti-tumor immunity through reduced immune suppression

Biochem Biophys Res Commun. 2022 Dec 17:634:100-107. doi: 10.1016/j.bbrc.2022.10.016. Epub 2022 Oct 6.

Authors

Jessica A Lapierre¹, Lauren A Geary¹, Julie K Jang², Alan L Epstein², Frank Hong³, Jean C Shih⁴

Affiliations

¹ Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Ave., Los Angeles, CA, USA; USC-Taiwan Center for Translational Research, University of Southern California, Los Angeles, CA, USA.
² Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
³ Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Ave., Los Angeles, CA, USA.
⁴ Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Ave., Los Angeles, CA, USA; USC-Taiwan Center for Translational Research, University of Southern California, Los Angeles, CA, USA; Department of Cell and Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Integrative Anatomical Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: jcshih@usc.edu.

PMID: 36242915
DOI: 10.1016/j.bbrc.2022.10.016

Abstract

We have previously shown that monoamine oxidase A (MAO A) mediates prostate cancer 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 cancer. Thus, MAO A inhibitor may alleviate immune suppression, increase the antitumor immune response and be used for cancer immunotherapy.

Keywords: Immune suppression; Monoamine oxidase A; Mouse model; Prostate cancer.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Cell Line, Tumor
Humans
Immunosuppression Therapy
Male
Mice
Monoamine Oxidase / genetics
Prostate* / pathology
Prostatic Neoplasms* / pathology
Tumor Microenvironment

Substances

Monoamine Oxidase

Grants and funding

P30 CA014089/CA/NCI NIH HHS/United States