Exploring Antitumor Immune Response in a Novel MLL3-Mutant Breast Cancer Model
Abstract
The research proposed here will directly address two overarching challenges facing breast cancer treatment: (i) identify what drives breast cancer growth; determine how to stop it, and (ii) revolutionize treatment regimens by replacing them with ones that are more effective and less toxic. Immunotherapies held great potential for cancer treatments that have long-lasting effects on eliminating cancer growth and dramatically improve patient survival. However, the success of such revolutionary therapies in breast cancers is still limited. This points to the existence of unknown mechanisms by which breast cancers can suppress tumor immunity. Gaining insights of these mechanisms is critical for successfully developing immunotherapies for breast cancer. To study these mechanisms, we need experimental systems that can closely mimic the tumor evolution process in human patients. To this end, we have developed a novel approach that allows us to rapidly generate mouse tumor models that are driven by the exact same human cancer gene mutations and to study how these mutations alter and suppress the immune system. Using this novel platform, we have discovered that frequently occurring mutations in a gene called MLL3 have the ability to promote tumor growth and potently suppress the effector functions of immune cells within the breast tumors. Our study will investigate and elucidate the underpinning mechanisms by which MLL3 mutations promote tumor development and cause immune suppression in tumors. Harnessing these mechanistic understandings, long-term goals will develop novel immunotherapeutic strategies for MLL3 mutant cancers by restoring the antitumor function of immune cells. MLL3 gene alterations occur in 8%-27% of human breast cancers, and these patients have particularly poor clinical outcome. Thus, successful outcomes of our study will have a major impact on improving breast cancer patient survival.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710512
Entities
People
- Wenjun Guo
Organizations
- Albert Einstein College of Medicine
- United States Army