Reprogramming Human Cancer Cells into Antigen Presentation

Cancer progression entails close crosstalk between tumor cells and immune system. Recent advances in understanding mutual tumor-immune interactions translated into the development of cancer immunotherapy, changing the cancer treatment paradigm. Nevertheless, despite achieving long-term effect even in advanced malignancies, only a minor subset of patients responds to immunotherapy. The activation of the immune system, as well as good response to the immunotherapy strongly depends on tumor immunogenicity and effective presentation of tumor-associated antigens by conventional dendritic cells type 1 (cDC1). However, downregulation of antigen-presentation machinery and cDC1 exclusion represent major mechanisms of cancer immune evasion, leading to immunotherapy failure. Previously, we identified a combination of 3 transcription factors, PU.1, IRF8, and BATF3 (PIB) that instructed direct reprogramming of fibroblasts into cDC1-like cells endowed with the ability to present and cross-present antigens. Here, we hypothesize that cDC1-direct reprogramming employing PIB transcription factors can impose antigen-presentation directly in human tumor cells, generating functional tumor-antigen presenting cells (tumor-APCs) able to prime antigen-specific T cell responses.