Cellular polarity pilots breast cancer progression and immunosuppression

Disrupted cellular polarity (DCP) is a hallmark of solid cancer, the malignant disease of epithelial tissues, which occupies ~90% of all human cancers. DCP has been identified to affect not only the cancer cell's aggressive behavior but also the migration and infiltration of immune cells, although the precise mechanism of DCP-affected tumor-immune cell interaction remains unclear. This review discusses immunosuppressive tumor microenvironments (TME) caused by DCP-driven tumor cell proliferation with DCP-impaired immune cell functions. We will revisit the fundamental roles of cell polarity (CP) proteins in sustaining mammary luminal homeostasis, epithelial transformation, and breast cancer progression. Then, the current data on CP involvement in immune cell activation, maturation, migration, and tumor infiltration are evaluated. The CP status on the immune effector cells and their targeted tumor cells are highlighted in tumor immune regulation, including the antigen presentation and the formation of immune synapses (IS). CP-regulated antigen presentation and delivery and the formation of IS between the immune cells, especially between the immune effectors and tumor cells, will be addressed. Alterations of CP on the tumor cells, infiltrated immune effector cells, or both are discussed with these aspects. We conclude that CP-mediated tumor aggressiveness coupled with DCP-impaired immune cell disability may decide the degree of immunosuppressive status and responsiveness to immune checkpoint blockade (ICB). Further elucidating the dynamics of CP- or DCP-mediated immune regulation in TME will provide more critical insights into tumor-immune cell dynamics, which is required to invent more effective approaches for cancer immunotherapy.