research

The mainstay of therapy for melanoma in recent years has been PD-1 inhibitors. However, not all patients respond, and many develop resistance over time. The lab is engaged in a number of projects using immune competent murine melanoma models developed by collaborators at Yale to study novel cytokines and co-inhibitory or co-stimulatory molecules. Bench-to-bedside evaluation of new drugs and drug regimens is conducted in the melanoma clinic, including investigator-initiated studies with deep interrogation of human samples.

As is the case with melanoma, not all renal cell carcinoma patients respond to anti-PD-1 with or without anti-CTLA-4. Studies of renal cell carcinoma are limited by a paucity of tractable murine models with clinically relevant genetics. In recent years we have also studied the tumor immune microenvironment in renal cell tumors and have found substantial differences from melanoma. Many of the drugs and approaches being studied in melanoma are also studied in mice bearing renal cell tumors and in patients with kidney cancer. 

Melanoma is the solid tumor with the highest propensity for brain homing, and approximately 15% of patients with renal cell carcinoma develop brain metastases at some point in the course of their illness. For over a decade we have studied molecules associated with cerebrotropism. We conduct both pre-clinical and clinical studies of brain metastases, with a focus on immunotherapy for brain metastases and molecules that modulate neovasculature in the central nervous system. 

While immunotherapy can induce durable responses in patients with advanced cancer, it is hampered by unpredictable and potentially morbid adverse events, which are poorly understood. The lab prospectively collects samples on all patients treated with immunotherapy in the Skin and Kidney Cancer Division, which are interrogated via various platforms for germline genetic predisposing factors, novel auto-antibodies and tissue infiltrating T cells.