University of Pennsylvania
Professor, Radiation Oncology
Director, Mark Foundation Center for Immunotherapy, Immune Signaling, and Radiation
Improving resistance to immunotherapies in breast cancer by targeting chronic inflammation.
Immunotherapy harnesses the power of the immune system to fight cancer. It is one of the most significant recent advances in cancer medicine. For breast cancer, immune checkpoint blockade, which prevents cancer cells from suppressing the immune cells trying to fight them, has demonstrated activity for certain subtypes such as triple-negative breast cancers. However, efficacy has unfortunately been lower compared to cancers such as melanoma and lung cancer. Research is urgently needed to uncover why breast cancer is resistant to immunotherapy, how to make it more susceptible, and how that can inform novel therapeutic strategies for patients.
Dr. Minn is investigating the idea that cancer cells can mimic certain features typically associated with chronic viral infections in order to minimize immune-mediated attacks, similar to how viruses can evade the immune system. A large percentage of breast cancer tumors express anti-viral gene programs typically seen in a chronic virus infection. Dr. Minn hypothesizes that interfering with these anti-viral signaling pathways in breast cancer can restore immune function against cancer cells and improve the efficacy of immunotherapy. His research examines individual cells to see how combination strategies that block anti-viral pathways restore immune function.
He is focusing on interferon (IFN) signaling, a critical pathway in the human immune response, as a potential target to oppose the tumor’s immunosuppressive effects. Following viral infection, the human body triggers a complex regulatory system of innate and adaptive immune responses designed to defend against the virus. Dr. Minn has found that chronic type II IFN stimulation of cancer cells leads to acquisition of changes resembling “inflammatory memory” or an adaptive response that protects tissues from the detrimental effects of chronic inflammation. These findings suggest that cancer cells can co-opt this response to orchestrate immune evasion that results in immune checkpoint blockade resistance.
Dr. Minn will continue his studies by focusing on investigating whether inflammatory signaling pathways control the acquisition or maintenance of inflammatory memory and IFN-driven immune checkpoint blockade resistance. He and his team will also use novel genetic engineering tools to uncover deep mechanistic insight and discover new genetic targets for resistance driven by chronic inflammation.
The main goal for his team is to improve cancer immunotherapies by targeting chronic inflammatory signaling, which may be a major resistance mechanism for breast cancer.
Andy Minn, MD, PhD is a Professor in the Department of Radiation Oncology and an Investigator at the Abramson Family Cancer Research Institute at the University of Pennsylvania. He is also the Director of the Mark Foundation Center for Immunotherapy, Immune Signaling and Radiation and Project Member at the Parker Institute for Cancer Immunotherapy. He received his MD and PhD from the University of Chicago and completed his residency in radiation oncology and post-doctoral training at Memorial Sloan Kettering Cancer Center.
His laboratory is focused on understanding the regulation and function of anti-viral signaling pathways, such as interferon and pattern recognition receptors, in cancer progression, immunotherapy response, and immunomodulation. They have discovered that activation of anti-viral signaling is widespread across multiple cancer types and often involve nucleic acid sensing, endogenous RNAs, exosomes, and interferon networks. Thus, endogenous molecules that participate in “virus mimicry” are pervasive in human cancer. They are investigating how anti-viral and pattern recognition receptors are activated in cancer, both cell intrinsically and through the tumor microenvironment, and their functional significance).
The William P. Lauder Award
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