Posted October 21, 2014
Peter P. Lee, M.D., City of Hope Beckman Research Institute
Dysregulation of the immune system is an important consequence of cancer development and a major factor in the progression to metastatic disease. However, the specific mechanisms causing immune dysfunction in all cancers, including breast cancer, are poorly understood. Current immunotherapies for the treatment of breast cancer have had limited clinical success; thus, further understanding of the underlying mechanisms causing immune dysfunction could lead to the development of more effective treatment strategies. With support from an FY05 Era of Hope Scholar Award, Dr. Peter P. Lee has focused his research efforts toward understanding immune system dysregulation in breast cancer development/progression.
Dr. Lee utilized immune cell and tumor samples taken from three sites in breast cancer patients: tumor, peripheral blood, and tumor-draining lymph nodes (TDLNs). He analyzed these samples for immune cell - cancer cell interactions, including dysfunction in a specific immune cell molecular pathway called the interferon (IFN) signaling pathway, which is critical for immune cell activation. He found that IFN-induced signaling was reduced in the immune cells of breast cancer patients, at all clinical stages, in contrast with the immune cells of healthy individuals. Furthermore, when Dr. Lee investigated other molecular gene pathways known to interact with IFN signaling, he found defects, previously undescribed, in the immune proteins, or interleukins, of breast cancer patients. He then studied the dynamics between breast cancer and immune responses by comparing gene expression patterns from TDLNs within the tumor site versus peripheral blood. Through this analysis, he identified different gene expression patterns between the two and observed an upregulation of gene signatures associated with tumor-promoting immune cells within the tumor site.
Taken together, these results show for the first time that immune cell regulation by IFN-induced gene signaling is deregulated in breast cancer patients. Dr. Lee received further funding from an FY11 Era of Hope Scholar Expansion Award and continues his work to elucidate the mechanisms of immune dysfunction in breast cancer. Additional understanding of these mechanisms may lead to novel strategies that can correct dysfunction and potentially enhance the success of current immunotherapeutic strategies for breast cancer.
Chang AY, Bhattacharya N, Mu J, Setiadi AF, Carcamo-Cavazos V, Lee GH, Simons DL, Yadegarynia S, Hemati K, Kapelner A, Ming Z, Drag DN, Schwartz EJ, Chen DZ, Lee PP. Spatial organization of dendritic cells within tumor draining lymph nodes impacts clinical outcome in breast cancer patients. J Transl Med. 2013 Oct 2;11:242.
Setiadi AF, Ray NC, Kohrt HE, Kapelner A, Carcamo-Cavazos V, Levic EB, Yadegarynia S, van der Loos CM, Schwartz EJ, Holmes S, and Lee PP. Quantitative, architectural analysis of immune cell subsets in tumor-draining lymph nodes from breast cancer patients and healthy lymph nodes. PLoS One 2010 Aug 25;5(8):e12420.