Actin cytoskeleton remodeling in tumor immune evasion - mechanisticaspects

A better understanding of the fundamental mechanisms underlying tumor immune evasion is critically for the development of new immunotherapystrategies aimed to restore/stimulate effective antitumor immune response in a larger number of patients. We previously reported a pivotal role for the actincytoskeleton in mediating cancer cell resistance to natural killer (NK) cell-induced cell death. We showed that, upon NK cell attack, a massiveaccumulation of actin near the immunological synapse (the interface between the NK cell and its target) rapidly takes place in resistant tumor cells. Wetermed this process "actin response" and provided evidence that it protects NK cell-conjugated target cells from undergoing apoptosis by preventingintracellular accumulation of NK cell-secreted cytotoxic molecules. Recently, we established that the actin response is a fundamental feature of immuneevasion conserved across different malignancies and induced in response to AG-specific cytotoxic T lymphocyte attack. However, the mechanismunderlying actin response-mediated immune evasion remains unclear. Based on our unpublished data, we will explore the possibility that the actinresponse acts as a "physical barrier" altering the structure and activity of the immunological synapse. Using state-of-the-art live cell imaging approaches,we will depict the structural and functional immunological defects caused by the actin response during the early steps of immune effector cell-tumor cellinteraction, such as alterations of the immunological synapse organization and increase of inhibitory immune checkpoint molecule density at the cell-cellcontact points. Finally, we aim at examining the prevalence of the actin response in pathological sample