PROJECT SUMMARY This study investigates the ‘reactive’ immune system in tumors, namely the cellular and molecular allies that allow immunotherapies to work. In particular it studies cells called ‘cDC1’. The overall hypothesis of this proposal is that a molecule called Granulin functions to regulate immunity in tumors, through its expression in these cells. This program is unique in applying spatial transcriptomics together with genetic tools and conventional cellular immunoassay methods to understand the critical phenotype-biology relationship between critical cDC populations and their partners. The resultant discoveries will be formative for designing new ways to boost anti- tumor immunity.