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Phospholipid Messengers as Drivers of Dendritic Cell Dysfunction in Cancer

Investigator

Juan R. Cubillos-Ruiz, PhD
Assistant Professor of Microbiology and Immunology in Obstetrics and Gynecology
Weill Cornell Medicine
New York, New York

Summary

In 2016 it is estimated that more than 22,000 women will be diagnosed with ovarian cancer and over 14,000 will die from the disease. Novel and more effective therapeutic strategies are urgently needed in the clinic to improve the dismal prognosis of this devastating disease. A form of immunotherapy, adoptive T cell therapy, utilizes immune cells called T cells that are engineered in the laboratory to recognize and eliminate cancer cells. This type of immunotherapy has been used successfully in melanoma patients, however, there has only been partial success in ovarian cancer. This is thought to be because the ovarian tumor microenvironment, the cells and structures that surround and support the cancer cells, work to suppress T cell activity. Preliminary evidence from the Cubillos-Ruiz group has confirmed that dendritic cells, another type of immune cell that is common in the tumor environment, are programmed in such a way that they inhibit T cell function. This proposal aims to understand how dendritic cell signaling is altered in ovarian cancer tumors. Specifically, a novel immunosuppressive pathway driven by a unique class of molecules, called lipid messengers, will be characterized in the dendritic cells of the tumor environment. The hypothesis is that these lipids cause severe immune cell dysfunction which would limit the clinical benefit of adoptive cell therapy in ovarian cancer. Therefore, this proposal will also determine if blocking the activity of these immunoregulatory lipids could provide a new approach to improve the effectiveness of ovarian cancer immunotherapies.

Updated: May 2016