Tumor immunology, cytokines, innate immunity
Our laboratory is interested in how the innate immune system recognizes developing tumor cells. Toward this end, we have generated a bank of tumor cell lines which we believe are enriched in recognition structures that activate innate immune components, including natural killer (NK) cells and macrophages. We hope to understand the molecular basis of this recognition.
We also have focused on a family of ligands for the NK cell receptor NKG2D. These NKG2D ligands are highly expressed on tumors, virally infected cells, and in certain autoimmune diseased tissues. We have shown that the NKG2D ligand H60 is regulated by the interferons and may function in this aspect to modulate the immune system. We are actively pursuing the regulation of H60 during carcinogenesis in order to understand how recognition structures might be acquired during the transformation process.
A related interest is in how T-regulatory cells inhibit the immune response to tumors. We have shown that these cells accumulate in both progressively growing and rejecting tumors. We plan to identify the mechanisms by which T-regulatory cells become activated in certain tumors for clinical benefit.
Bui, J.D., Carayannopoulos, L.N., Lanier, L.L., Yokoyama, W.M., and Schreiber, R.D. IFN-Dependent Down-Regulation of the NKG2D Ligand H60 on Tumors. Journal of Immunology 176 (2):905-13, 2006.
Bui, J.D., Uppaluri, R., Hsieh, C., and Schreiber, R.D. Comparative analysis of regulatory and effector T cells in progressively growing versus rejecting tumors of similar origins. Cancer Res. 2006 Jul 15;66(14):7301-9.
Bui, J.D. and Schreiber, R.D. Cancer Immunosurveillance, immunoediting, and inflammation :Independent or interdependent processes? Current Opinion in Immunology. 2007, 19(2):203-8.
Yadav, D., Ngolab, J., Lim, R., Krishnamurthy, S., Bui, J.D. Down-regulation of major histocompatibility complex class I-related chain A (MICA) on tumor cells by IFNγ-induced microRNA. Journal of Immunology 2009; 182 (1): 39-43.
Buchau, A., Morizane, S., Trowbridge, J., Schauber, J., Kotol, P., Bui, J.D., and Gallo, R.L. The host defense peptide cathelicidin is required for NK cell-mediated suppression of tumor growth. Journal of Immunology 2010; 184(1):369-78.
Zhang, H., Hardamon, C., Sagoe, B., Ngolab, J., Bui, J.D. Studies of the H60a locus in C57BL/6 and 129/Sv mouse strains identify the H60a 3’UTR as a regulator of H60a expression. Mol Immunol 2011; 48(4):539-45.
Yadav, D., Ngolab, J., Dang, N., Bui, J.D. Studies on the antigenicity of the NKG2D ligand H60a in tumour cells. Immunology 2011; 133(2):197-205.
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