PHILADELPHIA, PA — The Wistar Institute has made a significant breakthrough in understanding the role of Parkin, a protein traditionally associated with Parkinson’s disease, in the body’s immune response to cancer. Led by President and CEO Dr. Dario C. Altieri, the research offers new insights into how Parkin can suppress tumor traits and activate innate immune responses, presenting potential new avenues for cancer treatment.
Published in The Journal of Clinical Investigation, the study revealed that Parkin, often not expressed in various cancers, contributes to the production of interferons. These proteins are crucial in activating and attracting T cells to eradicate tumors. By engineering cancer cells to re-express Parkin, the research demonstrated its ability to stimulate immune responses, marking a pioneering discovery in cancer biology.
“Parkin has only recently been implicated for its role in cancer,” stated Dr. Altieri. “Our study adds to the knowledge base around that role. We are the first to demonstrate its dual function in both suppressing tumor traits and activating innate immunity.” This dual role highlights Parkin’s potential as a target for cancer therapies, particularly in cancers where its expression is epigenetically silenced.
Parkin is well-known for breaking down damaged proteins, a function impaired in Parkinson’s disease due to mutations in the PRKN gene. However, in cancer, Parkin can be epigenetically silenced by DNA methylation, a process that prevents gene expression. The research team, including an international cohort of scientists, reintroduced Parkin into tumor cells both in vitro and in vivo, observing that its presence led to increased interferon production and subsequent recruitment of anti-cancer T cells.
Further experiments involved restoring PRKN expression in mice using decitabine, a demethylating agent. This approach successfully reinstated Parkin expression, slowing tumor growth and enhancing immune response. “By reactivating Parkin, it may be possible to develop new treatment options and boost the immune system’s ability to fight cancer,” added Dr. Michela Perego, the study’s first author.
The research also included contributions from notable scientists such as Chiara Camisaschi, Nathalie Grandvaux, and Marcus Ruscetti, along with several others from The Wistar Institute. Supported by multiple NIH grants, this study opens new pathways for integrating Parkin reactivation in cancer therapy, offering hope for more effective treatments.
The findings highlight the potential of targeting Parkin to amplify the body’s natural immune responses against cancer, providing a promising strategy to enhance current cancer therapies. With the new understanding of Parkin’s role in immune modulation, researchers are optimistic about developing innovative treatments that could significantly improve patient outcomes in the battle against cancer.
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