Filipe Pereira and team are awarded with the Pfizer Award for Basic Research

The research study “Restoring tumor immunogenicity with dendritic cell reprogramming” was awarded with the Pfizer Award for Basic Research. The findings depicted in the Science Immunology publication in 2023 reported a strategy to overcome tumor evasion mechanisms by the cell fate reprogramming of tumor cells into dendritic cells.

Our immune system wages a battle against cancer, relying on mechanisms to identify and eliminate tumors cells. However, it is not a fair fight; tumor cells develop strategies to hide from immune cells and evade killing by our immune system. Dendritic cells mediate antitumor immunity and excel at processing and presenting antigens. With the Pereira Lab strategy, antitumor immunity had another string to their bow. Our research was based on the fact that cell identity can be converted from any identity to a known one – a process called cellular reprogramming. Since we have previously identified the transcription factors that impose a type 1 conventional dendritic cell identity (PU.1, IRF8, and BATF3), we were able to reprogram mouse and human cancer cells into antigen-presenting cells (APCs). Hence, tumor cells converted into tumor-APCs, which presented similar characteristics to dendritic cells, promoted immune recognition, and the elimination of cancer cells. Particularly, reprogramming into tumor-APCs allowed the presentation of endogenous tumor antigens on MHC-I and facilitated targeted killing by CD8+ T cells. Functionally, tumor-APCs engulfed and processed proteins and dead cells, secreted inflammatory cytokines, and cross-presented antigens to naïve CD8+ T cells. In mice, injecting tumor-APCs in tumors decreased tumor growth, increased survival, and ameliorated the response to immune checkpoint blockade.

These findings show that reprogramming enforces antigen presentation, overcomes tumor evasion mechanisms, and enhances antitumor immunity. Converting tumor cells into professional immune cells is an innovative therapeutic alternative setting the stage for the development of a novel cancer immunotherapy modality.

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