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Complex immune evasion mechanisms and lack of biomarkers predicting responsiveness to immune checkpoint blockade therapies compromise immunotherapy’s therapeutic efficacy for patients with prostate cancer. The authors review established and nominated immune evasion mechanisms in prostate cancer and discuss how the precise treatment strategies can be developed to improve efficacy of immunotherapy.

During gastrulation of the mouse embryo, individual cells ingress in an apparently stochastic pattern during the epithelial-to-mesenchymal transition (EMT). Here we define a critical role of the apical protein Crumbs2 (CRB2) in the gastrulation EMT. Static and live imaging show that ingressing cells in Crumbs2 mutant embryos become trapped at the primitive streak, where they continue to express the epiblast transcription factor SOX2 and retain thin E-cadherin-containing connections to the epiblast surface that trap them at the streak. CRB2 is distributed in a complex anisotropic pattern on apical cell edges, and the level of CRB2 on a cell edge is inversely correlated with the level of myosin IIB. The data suggest that the distributions of CRB2 and myosin IIB define which cells will ingress, and we propose that cells with high apical CRB2 are basally extruded from the epiblast by neighbouring cells with high levels of apical myosin.

Collective cell migration is a key process during epithelial morphogenesis, tissue regeneration and tumor dissemination. During collective epithelial migration, anterior-posterior polarity, apical-basal polarity and cell-cell junctions must be dynamically coordinated, but the underlying molecular mechanisms controlling this complex behavior are unclear. Rho GTPases regulate the actin cytoskeleton, in particular protrusive and contractile activities at cell-cell contacts. Recently, a number of regulators - nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) - have been identified and suggested to provide spatio-temporal control of Rho GTPases at cell-cell contacts. One of these is myosin IXA, a member of class IX, single-headed actin motors having a conserved RhoGAP domain. Using its actin-binding and motor activities, myosin IX interacts with actin filaments and moves toward filament plus ends. At the plasma membrane, myosin IX’s RhoGAP activity negatively regulates Rho to facilitate localized reorganization of the actin cytoskeleton. Here, I discuss how myosin IXA regulates Rho and the actin cytoskeleton during the assembly of nascent cell-cell contacts and how this might contribute to collective epithelial migration.