held in partnership with the Society for Immunotherapy of Cancer

The immunosuppressive tumor microenvironment per-turbs numerous immune regulatory networks and usurps host antitumor immunity. We discovered that tumor interferes with host hematopoietic Notch system in lung cancer patients [1]. The resultant decrease in immune Notch signaling could be a major causative link in the inadequate induction of antitumor immunity. Interestingly, administration of the novel Delta-like ligand 1 (DLL1) multivalent cluster [1] and the FDA-approved proteasome inhibitor drug bortezomib, which also sensitizes tumors to death signals [2,3], restored the tumor-induced decrease in immune Notch. Bortezomib increased the expression of Notch target genes Hes1 and Hey1 in thymus, lymph node, and spleen of tumor-bearing mice. Moreover, bortezomib administratio