In vivo dendritic cell reprogramming for cancer immunotherapy [organoid scRNA]

Immunotherapy can lead to long-term survival for some cancer patients, yet generalized success has been hampered by insufficient antigen presentation and exclusion of immunogenic cells from the tumor microenvironment. Here, we developed an approach to reprogram tumor cells in vivo by adenoviral delivery of the transcription factors PU.1, IRF8, and BATF3, which enabled them to present antigens as type 1 conventional dendritic cells. Reprogrammed tumor cells remodeled their tumor microenvironment, recruited, and expanded polyclonal cytotoxic T cells, induced tumor regressions, and established long-term systemic immunity in multiple mouse melanoma models. In human tumor spheroids and xenografts, reprogramming to immunogenic dendritic-like cells progressed independently of immunosuppression, which usually limits immunotherapy. Our study paves the way for human clinical trials of in vivo immune cell reprogramming for cancer immunotherapy. Overall design: To verify that a cDC1 program was established in cancer spheroids and to uncover potential differences in cDC1 reprogramming progressing in 2D or 3D cultures, we FACS-purified CD45+ and HLA-DR+ T98G cells at days 3, 7, and 9 of reprogramming and performed scRNA-seq. This submission includes only 2 of the 2D samples (day 7 and day9). We used 2 of the 2D samples (day 0 and day3) from previous submission GSE224941 (GSM7035968, GSM7035969).