The University of Texas MD Anderson Cancer Center
Department of Immunology
The immune system shapes the development and progression of cancer through a process called cancer immunoediting. In certain circumstances, it functions as an extrinsic tumor suppressor by either destroying highly antigenic tumor cells (elimination) or holding them in a state of immune-mediated quiescence (equilibrium). However, cancer cells may also evade immune destruction (escape) thus manifesting as the disease of cancer. These outgrown escape tumors display reduced immunogenicity and establish an immunosuppressive environment often mediated by negative regulators of T cell activation, which may be reversed with immune checkpoint therapy (e.g., anti-CTLA-4/anti-PD-1).
Cancer mutations that form tumor-specific neoantigens often drives the process of immunoediting and may be targets of T cells reactivated by immune checkpoint therapy. The means by which tumors become edited and escape immune regulation depend not only on the type and potency of T cell antigens but also the microenvironment and tissue of tumor derivation, ultimately impacting effectiveness of therapy. Using both transplant tumor models and genetically engineered mouse models of primary and metastatic cancer, we seek to better understand the process of immunoediting during metastasis and develop novel treatment strategies effective against primary and metastatic tumors.
Our lab has several highly integrated projects towards the goal of making cancer immunotherapy safer, more specific, and more effective to increasing numbers of patients. These studies include: (a) Defining T cell responses to tumor-specific neoantigens and tumor-associated antigens in primary, as well as metastatic tumors; (b) Development of tumor neoantigen-specific vaccines (used alone or in combination with other therapies) effective against primary and metastatic cancers; (c) Understanding transcriptional regulation of anti-tumor cytotoxic CD8+ T cells; and (d) High dimensional analyses (e.g., CyTOF and single-cell RNA sequencing) of intratumoral immune cells to better define successful and unsuccessful immunotherapies in metastatic cancers.
Education & Training
Ph.D., University of Missouri, 2012