Metadherin Promotes Triple-Negative Breast Cancer Progression and Metastasis by Inducing Immune Evasion

Abstract

Patients with triple negative breast cancer (TNBC) exhibit poor prognosis and have limited treatment options. Recently, immunotherapies have shown improved clinical response and survival, but many patients show resistance and limited improvement. Understanding differences in these patients’ molecular markers will aid in elucidating mechanisms of immune escape and proposing new targets for treatment. Metadherin (MTDH) has previously been reported as a molecular marker to predict prognosis of TNBC. However, how MTDH regulates TNBC progression and metastasis is still largely unknown. In this study we utilize a murine tumor cell and immune cell co-culture platform coupled with a CRISPR-dCas9 activation screen to identify novel candidate genes that account for MTDH’s function in TNBC. Our results indicate that MTDH promotes TNBC progression and metastasis by enhancing immune evasion. Mechanistically, LITAF and NOXP20 may function in association with MTDH to confer tumor cells with immunosuppressive potential. We also propose further study of the LITAF-NOXP20-MTDH signaling axis and mechanistic validation of interactions and downstream effects. Understanding how these proteins influence immune regulation and evasion of immune defense will open up new territory for predicting response and improving prognosis. Equal accessibility and awareness of these novel treatments will improve prognosis and survival rates in all breast cancer patients.