Evanthia Roussos Torres, MD/PhD, Keck School of Medicine of USC
Assistant Professor of Medicine and Cancer Biology, Division of Oncology
Co-Leader Tumor Immune Microenvironment Program
Co-Leader Tumor Immune Microenvironment Program
Project: Determine organ specific immunosuppressive effects on immune activation and breast cancer progression
Immunotherapy works by re-training the body's immune system to fight cancer. This type of therapy holds great promise to help people with both early stage and metastatic breast cancer (MBC) live longer with fewer side effects and decreased toxicity from ongoing therapy or progressive disease. When people get sick, the body’s immune system works to recognize foreign cells causing infection and kills them. However, in the case of cancer, the tumor cells send signals to the body to suppress the immune system thus, preventing tumor elimination. Eventually, the lack of immune response enables tumor growth and, in many cases, spread to distant organs. One goal of immunotherapy is to revitalize the body’s natural immune response and significantly prolong the lives of patients without the toxicity of traditional chemotherapy. Another goal of immunotherapy is to create a durable treatment response, a response that continues to work against the tumor even after treatment has stopped. This works by utilizing immune checkpoint inhibitors (ICIs) to promote this lasting anti-tumor immune response. These therapies have revolutionized cancer therapy and were the topic of research that led to a Nobel Prize awarded to Drs. Allison and Honjo in 2018. It is my hope that a better understanding of how the suppression of the immune response works will allow us to find treatments that will control this suppression and improve patient response to ICIs. This is an umet need since we currently don’t have drugs to target immune suppression prior to use of ICIs and as a result we only see success of ICIs in a small percentage of patients with breast cancer. We also do not currently personalize use of ICIs by site of metastatic disease in which patients are progressing. It is my hope that because of this research, we can expand the patient population who can benefit from these medications, and decrease toxicity from traditional therapies, to improve quality of life and longevity.
The studies I propose will determine the potential mechanism of resistance within different sites of disease such as the breast, where the cancers originate, and the lung, and liver, where breast cancers often spread. The Roussos Torres lab has been successful in our initial research investigating novel therapeutic combinations that achieve improved responses to ICIs as described in her recent publication reporting the results of a clinical trial, NCI-9844- combined therapy with entinostat, nivolumab + ipilimumab demonstrated responses in patients with metastatic breast cancer. She also published two other studies that investigated the mechanism of response to this therapy that supports and provide a premise for her ongoing investigations. She has designed experiments that will now investigate if suppressor cells within breast tumors differ from those that have metastasized to the lung or the liver. This will help us to understand if certain sites of metastases are more amenable to treatment modulating immune suppression and as a result more likely to benefit from such therapies. This will facilitate a more personalized approach to treatment of breast cancer. Secondly, she will work in collaboration with computational biologists to adapt a math model to account for differences in immune cells at different metastatic sites and test if this model can predict disease progression. Once validated, use of the math model will allow faster prediction of site-specific progression of metastatic disease and therapeutic response. The model will be adapted to assess changes in growth of metastatic target lesions. This will be tested in prospective clinical trials as a potential tool for prediction of response.
There are no current treatment strategies informed by progression of disease at specific locations or by targeting immune suppression to improve tumor killing by checkpoint therapies. Integration of outcomes produced by these cutting-edge technologies, with mathematical modeling will accelerate discovery enabling better outcomes for people with breast cancer.
Your contributions will not only help support the materials needed to complete this work which includes both collection of patient biospecimens—blood and tissue, and lab materials, but will also help support the incredibly dedicated team that makes this work happen. To be successful, we have a very diverse group of individuals which range from research coordinators, graduate students, lab technicians and administrative program coordinators. Without this group we would not be as successful as we have been in moving our work forward.
Immunotherapy works by re-training the body's immune system to fight cancer. This type of therapy holds great promise to help people with both early stage and metastatic breast cancer (MBC) live longer with fewer side effects and decreased toxicity from ongoing therapy or progressive disease. When people get sick, the body’s immune system works to recognize foreign cells causing infection and kills them. However, in the case of cancer, the tumor cells send signals to the body to suppress the immune system thus, preventing tumor elimination. Eventually, the lack of immune response enables tumor growth and, in many cases, spread to distant organs. One goal of immunotherapy is to revitalize the body’s natural immune response and significantly prolong the lives of patients without the toxicity of traditional chemotherapy. Another goal of immunotherapy is to create a durable treatment response, a response that continues to work against the tumor even after treatment has stopped. This works by utilizing immune checkpoint inhibitors (ICIs) to promote this lasting anti-tumor immune response. These therapies have revolutionized cancer therapy and were the topic of research that led to a Nobel Prize awarded to Drs. Allison and Honjo in 2018. It is my hope that a better understanding of how the suppression of the immune response works will allow us to find treatments that will control this suppression and improve patient response to ICIs. This is an umet need since we currently don’t have drugs to target immune suppression prior to use of ICIs and as a result we only see success of ICIs in a small percentage of patients with breast cancer. We also do not currently personalize use of ICIs by site of metastatic disease in which patients are progressing. It is my hope that because of this research, we can expand the patient population who can benefit from these medications, and decrease toxicity from traditional therapies, to improve quality of life and longevity.
The studies I propose will determine the potential mechanism of resistance within different sites of disease such as the breast, where the cancers originate, and the lung, and liver, where breast cancers often spread. The Roussos Torres lab has been successful in our initial research investigating novel therapeutic combinations that achieve improved responses to ICIs as described in her recent publication reporting the results of a clinical trial, NCI-9844- combined therapy with entinostat, nivolumab + ipilimumab demonstrated responses in patients with metastatic breast cancer. She also published two other studies that investigated the mechanism of response to this therapy that supports and provide a premise for her ongoing investigations. She has designed experiments that will now investigate if suppressor cells within breast tumors differ from those that have metastasized to the lung or the liver. This will help us to understand if certain sites of metastases are more amenable to treatment modulating immune suppression and as a result more likely to benefit from such therapies. This will facilitate a more personalized approach to treatment of breast cancer. Secondly, she will work in collaboration with computational biologists to adapt a math model to account for differences in immune cells at different metastatic sites and test if this model can predict disease progression. Once validated, use of the math model will allow faster prediction of site-specific progression of metastatic disease and therapeutic response. The model will be adapted to assess changes in growth of metastatic target lesions. This will be tested in prospective clinical trials as a potential tool for prediction of response.
There are no current treatment strategies informed by progression of disease at specific locations or by targeting immune suppression to improve tumor killing by checkpoint therapies. Integration of outcomes produced by these cutting-edge technologies, with mathematical modeling will accelerate discovery enabling better outcomes for people with breast cancer.
Your contributions will not only help support the materials needed to complete this work which includes both collection of patient biospecimens—blood and tissue, and lab materials, but will also help support the incredibly dedicated team that makes this work happen. To be successful, we have a very diverse group of individuals which range from research coordinators, graduate students, lab technicians and administrative program coordinators. Without this group we would not be as successful as we have been in moving our work forward.
