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In vivo dendritic cell reprogramming for cancer immunotherapy [T cell scRNA + TCR]

ABSTRACT: In vivo dendritic cell reprogramming for cancer immunotherapy [T cell scRNA + TCR]

PROVIDER: PRJNA1074791 | ENA |

REPOSITORIES: ENA

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In vivo dendritic cell reprogramming for cancer immunotherapy [T cell scRNA + TCR]

Project description: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.

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Project description:Epicutaneous immunotherapy (EPIT) protocols have recently been developed to restore tolerance in patients with food allergy (FA). The mechanisms by which EPIT protocols promote desensitization rely on a profound immune deviation of pathogenic T and B cell responses. To date, little is known about the contribution of skin dendritic cells (skDCs) to T cell remodelling and EPIT efficacy. Our results emphasize that the acquisition of distinct phenotypic and functional specializations by skDCs during EPIT is at the cornerstone of the desensitization process.

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