Research Projects

The field of tumor immunology has traditionally focused on T cell-mediated humoral immune responses, but recent evidence supports that humoral responses by tumor-infiltrating B-cells (TIL-B cells) are associated with immune protection in multiple human solid tumors. IgA is the most dominant class of immunoglobulin in human endometrial and ovarian cancer, and IgG antibodies are also observed to be spontaneously produced in both gynecological cancer types studied. However, in many cancers, such as breast cancer, IgG antibodies are the predominant class of immunoglobulin produced at tumor beds. A foundational study is proposed to understand how primary cancer tissues bypass the anti-tumor functions of the spontaneous IgG antibodies produced naturally by TIL-B cells at tumor beds. The central hypothesis is that Neonatal Fc Receptor (FcRn) sequesters IgG antibodies and abrogates the anti-tumor functions of IgG antibodies produced by tumor infiltrating plasma cell B lymphocytes. This hypothesis is based on preliminary observations that Neonatal Fc Receptor is expressed quasi-universally by most epithelial cancer tissues and many non-epithelial cancers. Experiments using clinical specimens, in vivo models, and in vitro settings will uncover the role of expression of FcRn by cancer cells and provide insights into future therapeutic targets applicable to multiple cancer types.