Simon A. Grassmann, MD, Donald J. Gogel Postdoctoral Fellow Memorial Sloan Kettering Cancer Center Area of Research: All Cancers Immune cells such as CD8+ T cells and Natural Killer (NK) cells can recognize mutated cells and elicit an immune response against tumors. Thereby, the immune system is in principle capable of rejecting even advanced tumors. However, tumors develop strategies to suppress the immune system and thus prevent being targeted by CD8+ T cells and NK cells. Cancer immunotherapy seeks to undo this immunosuppression by the tumor. Some tumors are thought to hijack NK cells so that they do not kill tumor cells but potentially even promote tumor growth. In order to reverse this tumor-mediated NK cell suppression, it is essential to identify the exact mechanisms by which the tumor achieves its goal. In this proposal, Dr. Grassman will use novel technologies to follow the fate of individual NK cells. His goal is to understand how the tumor influences and modulates individual NK cells. Often, tumors drive immune cell suppression by expressing signal molecules that bind to the target cells and alter their function. One candidate signal is the cytokine IL-21 that binds to IL-21 receptor on tumor-infiltrating NK cells. To test whether this pathway is relevant for NK cell dysfunction in tumors, he will study how NK cells behave when they cannot express this IL-21 receptor. Altogether, this study will help develop therapies that prevent tumor-mediated NK cell suppression in patients, thus enabling a potent immune response against cancer. Projects and Grants Deciphering differentiation of intratumoral innate lymphocytes using single-cell fate mapping Memorial Sloan Kettering Cancer Center | All Cancers | 2021 | Joseph Sun, PhD
