The University of Texas MD Anderson Cancer Center
Department of Immunology
Tumors deploy genetic programs of both active immune suppression and passive immune privilege in order to establish, grow, and spread throughout the host. By discovering and reversing or circumventing these adaptations, even fully-established, metastatic tumors can be rejected immunologically. Activation of anti-tumor immunity through releasing negative regulation of T-cells (e.g. αCTLA-4/αPD-1) or direct functional stimulation (e.g. α4-1BB) has led to remarkable therapeutic responses in patients with melanoma including complete responses (CRs) even in patients with bulky metastatic disease. Despite these unprecedented examples of clinical benefit, however, the vast majority of human cancers remain resistant to antibody-mediated immunotherapy. Our studies of murine tumor models resistant to immunotherapy, such as pancreatic and prostatic adenocarcinoma, suggest that these tumors effectively prevent accumulation of tumor-specific T cells through establishment of inaccessible hypoxic cores, recruitment of myeloid suppressor cells, and establishment of dense stromal barriers lacking in relevant tumor antigens. By breaking down these microenvironmental barriers while at the same time augmenting anti-tumor immunity with T cell co-stimulatory antibodies, we hope to expand the range of cancers sensitive to immunotherapeutic rejection. Projects in the lab range from basic tumor immunology focused on discovering and overcoming novel mechanisms by which tumors evade immune rejection to translational biomarker studies where we apply mechanistic insights from our pre-clinical data to understand, using clinical samples, why some patients experience CRs while others progress on the same immunotherapy regimen.
Education & Training
Ph.D. - Stanford University Medical School - 2001