Multifactoral Immune Modulation Potentiates Durable Remission in Multiple Models of Aggressive Malignancy

Tumors typically lack canonical danger signals required to activate adaptive immunity and also frequently employ substantial immunomodulatory mechanisms that downregulate adaptive responses and contribute to escape from immune surveillance. Given the variety of mechanisms involved in shielding tumors from immune recognition, it is not surprising that single agent immunomodulatory approaches have been largely unsuccessful in generating durable antitumor responses. Here we report a unique combination of immunomodulatory and cytostatic agents that recondition the tumor microenvironment and eliminate complex and/or poor-prognosis tumor types including the aggressive MOC-2 model of HNSCC. scRNAseq analysis implicated up-regulation of innate immune responses and antigen presentation in tumor cells and the myeloid cell compartment as critical early events. Overall design: Single cell suspensions were generated from six MOC-2 tumor-bearing male mice at 24 hours after intratumoral drug or vehicle treatment. Live cells were isolated by FACS sorting. Each tumor sample was tagged with a Multiplexing Oligo (10x Genomics) and sequenced with NovaSeq X Plus PE150 by the Novogene Corporation. Data processing was performed using Cell Ranger v.7.1 and Seurat v4.1.0.