University of Michigan
NK Cell-mediated Immunotherapy against Lung Cancer
Millions of cells are estimated to shed into circulation by primary tumors, less than 0.1 percent of cells successfully spread to distant sites to establish metastases that is responsible for <90 percent of cancer deaths. To date, focus was on understanding how a small proportion of cells escape host immune surveillance to metastasize but not on the mechanisms by which immune system contributes to eradicate more than 99 percent of tumor cells. Based on strong preliminary data, we propose a novel mechanism by which a key immune cell type (natural Killer [NK] cells) present in the body specifically targets spreading tumor cells and prevent metastasis. Specific aims of this proposal are defining the role of a protein called CADMI that mediates this tumor cell killing by NK cells and testing strategies to enhance CADM1 expression in tumor cells and also to boost NK cell functions by modulating receptors that recognize CADM1, for the prevention of lung cancer metastasis.