Immune Response and Metastasis-Links between the Metastasis Driver MACC1 and Cancer Immune Escape Strategies

Simple Summary While both the fields of cancer metastasis research and cancer immunology have been heavily investigated, their combination-the immunology of metastasis-is underrepresented given the fact that metastasis is responsible for up to 90% of cancer deaths. Additionally, evading detection by the immune system is a key prerequisite for the spread of tumor cells to distant organs. In this review, we explore the connections between a master regulator of metastasis, MACC1, and both its direct and indirect links with immunological processes. Specifically, we highlight MACC1-induced alterations of signaling pathways and secreted factors and how this translates into changed immunological outcomes including effects on immune cell infiltration, activity, and their regulation through immunological checkpoints.Abstract Metastasis remains the most critical factor limiting patient survival and the most challenging part of cancer-targeted therapy. Identifying the causal drivers of metastasis and characterizing their properties in various key aspects of cancer biology is essential for the development of novel metastasis-targeting approaches. Metastasis-associated in colon cancer 1 (MACC1) is a prognostic and predictive biomarker that is now recognized in more than 20 cancer entities. Although MACC1 can already be linked with many hallmarks of cancer, one key process-the facilitation of immune evasion-remains poorly understood. In this review, we explore the direct and indirect links between MACC1 and the mechanisms of immune escape. Therein, we highlight the signaling pathways and secreted factors influenced by MACC1 as well as their effects on the infiltration and anti-tumor function of immune cells.