Olivera J. Finn, PhD
- Postdoc, Stanford University, 1980-1982
- PhD, Stanford University, 1980
Distinguished Professor, Department of Immunology
Distinguished Professor, Department of Surgery
Member, Graduate Program in Microbiology and Immunology (PMI)
The long-standing interests of our laboratory center on identifying specific mechanisms of human anti-tumor immunity and cancer immunosurveillance. We study T cell and antibody repertoire in cancer patients and in healthy individuals at risk for cancer and factors that influence that repertoire. We were the first to identify a human tumor antigen recognized by human T cells and antibodies, the epithelial mucin MUC1. We showed that tumors express an abnormal form of MUC1 that is recognized by the immune system as a foreign rather than a self-antigen. Studies in mice and primates showed that MUC1 was immunogenic and that anti-MUC1 immune responses can reject tumors. These studies supported multiple clinical trials of a MUC1 vaccine in patients with breast, colon and pancreatic cancer. Most recently, we began testing a MUC1 vaccine for cancer prevention in individuals diagnosed with MUC1+ premalignant lesions. In addition to being a tumor antigen, MUC1 is an oncogene by virtue of promoting a highly inflammatory tumor microenvironment. We discovered that the tumor form of MUC1 activates NF-kB, binds p65 and translocates to the tumor cell nucleus where it binds to and activates promoters of inflammatory cytokines, such as IL-6 and TNF-a. MUC1 has been associated with a more invasive cancer phenotype and we have recently deciphered the mechanism by showing that it forms complexes with CIN-85, also previously associated with cell motility and invasion.
While studying MUC1 and another tumor antigen that we discovered, cyclin B1, we made an important observation that many tumor associated antigens (TAA) described by their abnormal expression on cancer cells, are also abnormally expressed in other acute or chronic inflammatory conditions and are therefore more appropriately defined as disease associated antigens (DAA). These include bacterial infections such as Mumps, viral infections such as chicken pox, and chronic inflammations such as inflammatory bowel disease (IBD). This observation helped us formulate and test a new hypothesis on cancer immunosurveillance. Working in collaboration with epidemiologists and creating appropriate mouse models, we showed that immunity to abnormal self-antigens, DAAs, is generated simultaneously with immunity to pathogens early in life in the course of febrile infections. Immune memory for DAAs contributes to effective immunosurveillance of other pathogen infections throughout life, as well as of cancer that expresses many of those same antigens. Lastly, we are pursuing an idea that the quantity and the quality of immune memory for DAAs is critical for maintaining general immune health. Using genomic and bioinformatics approaches, we are defining a gene expression signature that characterizes individuals with strong immunosurveillance ability versus those that lack that ability and designing DAA-based vaccines to promote immunosurveillance of cancer and other diseases.
Iheagwara, U. K., P. L. Beatty, P. T. Van, T. M. Ross, J. S. Minden, and O. J. Finn. 2014. Influenza virus infection elicits protective antibodies and T cells specific for host cell antigens also expressed as tumor-associated antigens: a new view of cancer immunosurveillance. Cancer Immunol Res 2:263-273.
Finn, O. J. 2014. Vaccines for cancer prevention: a practical and feasible approach to the cancer epidemic. Cancer Immunol Res 2:708-713.
Farkas, A. M., and O. J. Finn. 2014. Novel mechanisms underlying the immediate and transient global tolerization of splenic dendritic cells after vaccination with a self-antigen. J Immunol 192:658-665.
Zhang, L., A. Vlad, C. Milcarek, and O. J. Finn. 2013. Human mucin MUC1 RNA undergoes different types of alternative splicing resulting in multiple isoforms. Cancer Immunol Immunother 62:423-435.
Kimura, T., J. R. McKolanis, L. A. Dzubinski, K. Islam, D. M. Potter, A. M. Salazar, R. E. Schoen, and O. J. Finn. 2013. MUC1 vaccine for individuals with advanced adenoma of the colon: a cancer immunoprevention feasibility study. Cancer Prev Res (Phila) 6:18-26.
Cascio, S., L. Zhang, and O. J. Finn. 2011. MUC1 protein expression in tumor cells regulates transcription of proinflammatory cytokines by forming a complex with nuclear factor-kappaB p65 and binding to cytokine promoters: importance of extracellular domain. J Biol Chem 286:42248-42256.
Cramer, D. W., A. F. Vitonis, S. P. Pinheiro, J. R. McKolanis, R. N. Fichorova, K. E. Brown, T. F. Hatchette, and O. J. Finn. 2010. Mumps and ovarian cancer: modern interpretation of an historic association. Cancer Causes Control 21:1193-1201.
Beatty, P. L., S. Narayanan, J. Gariepy, S. Ranganathan, and O. J. Finn. 2010. Vaccine against MUC1 antigen expressed in inflammatory bowel disease and cancer lessens colonic inflammation and prevents progression to colitis-associated colon cancer. Cancer Prev Res (Phila) 3:438-446.
Vella, L. A., M. Yu, S. R. Fuhrmann, M. El-Amine, D. E. Epperson, and O. J. Finn. 2009. Healthy individuals have T-cell and antibody responses to the tumor antigen cyclin B1 that when elicited in mice protect from cancer. Proc Natl Acad Sci U S A 106:14010-14015.