cIAP1/2 antagonism eliminates MHC class I negative tumors through T cell-dependent reprogramming of mononuclear phagocytes

Induction of non-canonical NF-kB signaling with IAP antagonists mimics costimulatory signaling, augmenting anti-tumor immunity. We now show that induction of non-canonical NF-kB signaling induces T-cell dependent immune responses even in B2M-null tumors, demonstrating that direct CD8 T cell recognition of tumor cell expressed MHC class I is not required. Instead, T cell-produced cytokines reprogram macrophages to be tumoricidal. In wildtype mice IAP antagonism reduces tumor burden by increasing phagocytosis of tumor cells. We characterized by RNA-Seq the transcriptional profile of intratumoral phagocytes with and without treatment with the IAP antagonist LCL161. Overall design: CD45+ CD11b+ cells were sorted by FACS from orthotopic 6694c2 pancreatic tumors implanted in C57BL/6 mice treated with vehicle or the IAP antagonist LCL161 for 12 days.