Harnessing Diverse Dendritic Cell Reprogramming for Immunotherapy

Cancer immunotherapy re-establishes the function of the immune system of recognizing tumour-associated neoantigens. Although many patients benefited from these forms of therapy, others have still proven resistant.
Dendritic cells (DCs), subdivided in type 1 (cDC1), 2 (cDC2) or plasmacytoid (pDC), are immune cells with important role in antigen-presentation, proven to be implicated in cancer immunosurveillance. Through cellular reprogramming, induced DCs have been previously generated from fibroblasts with the overexpression of different combinations of transcription factors.
Here, we evaluated the reprogramming of different melanoma and breast cancers (B16, Yumm1.7, EO771. PymT and BRAF) into multiple DC subsets in vitro and in vivo and investigated their antitumor effect. We found that Yumm1.7 exclusively responded to induced cDC1 while EO771 responded to induced cDC2 and pDC. By combining DC reprogramming we observed tumor-induced cDC2s in Yumm1.7 negatively affected the anti-tumorigenicity of tumor-induced cDC1s, while combined tumor-induced cDC2s and pDCs inhibited EO771 tumor growth.