Ph.D.
(1975) |
Edith
Lord
Professor of Oncology in Microbiology & Immunology Primary Appointment: GEBS Cluster Affiliations: |
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| Contact Information: | ||
| University
of Rochester School of Medicine and Dentistry 601 Elmwood Ave, Box 672 Rochester, New York 14642 |
Medical Center KMRB 2-9617(Office) / 2-9812(Lab) Phone: (585) 275-5855 Fax: (585) 473-9573 E-Mail: edith_lord@urmc.rochester.edu |
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- Research Focus
- Cell-Mediated Immunity to Tumors
- Research Overview
- We are interested in the immune responses, which can control tumor development and in how cells of the immune system access and function within the tumor microenvironment. Because of their rapid growth tumor cells require oxygen and other nutrients and thus have the ability to induce the formation of new blood vessels, a process known as angiogenesis. However, these vessels are often abnormal resulting in areas of low oxygen (hypoxic regions). Tumor cells in these areas are more resistance to conventional therapies such as radiation and chemotherapy and probably also to immunotherapy as it is more difficult for immune cells to infitrate into these regions. We are using a variety of murine tumor models to assess the interactions of immune cells and tumor cells within the unique environment of solid tumors.
- We have found that the cytokine, IL-12 in addition to affecting immune function also can severely limit the formation of blood vessels with tumors by suppressing the upregulation of a receptor for an important pro-angiogenic factor known as vascular endothelial growth factor. We are currently determining the molecular mechanisms involved in this process.
- In addition, we are studying how conventional tumor therapies, in particular radiation therapy, affect the immune response to tumors and how these modalities may be combined for more effective treatment. Radiation therapy alters the expression of adhesion molecules on tumor vessels, which appears to allow greater infiltration of host immune cells. Other studies are examining the use of the migration of antigen presenting cells in the skin as a measure of radiation exposure.
- A new project is examining a unique tissue within the peritioneal cavity known as the omentum, which is the initial site of metastases for tumors growing in this area. Interestingly, the metastatic tumor cells appear to attach preferentially to particular areas of this tissue, which contain high numbers of immune cells. We are currently studying the mechanisms of tumor attachment and growth in these areas.
- Recent Publications
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Sorensen EW, Gerber SA, Sedlacek AL, Rybalko VY, Chan WM, Lord EM Omental immune aggregates and tumor metastasis within the peritoneal cavity. Immunol Res. 2009 Feb 28;
Lugade, Aa, Sorensen, EW, Gerber, SA, Moran, JP, Frelinger, JG, Lord, EM. RADIATION-INDUCED IFN-gamma production within the tumor microenvironment influences antitumor immunity. J. Immunol. 180:3132-3139, 2008. - Santos K, Simon DA, Conway E, Bowers WJ, Mitra S, Foster TH, Lugade A, Lord EM, Federoff HJ, Dewhurst S, Frelinger JG. "Spatial and temporal expression of herpes simplex virus type 1 amplicon-encoded genes: implications for their use as immunization vectors." Hum Gene Ther.18:1-13, 2007.
- Ramanayake T, Simon DA, Frelinger JG, Lord EM, Robert J. In vivo study of T-cell responses to skin alloantigens in Xenopus using a novel whole-mount immunohistology method." Transplantation 83:159-66, 2007.
- Gerber SA, Rybalko VY, Bigelow CE, Lugade AA, Foster TH, Frelinger JG, Lord EM "Preferential attachment of peritoneal tumor metastases to omental immune aggregates and possible role of a unique vascular microenvironment in metastatic survival and growth." Am J Pathol. 169:1739-52, 2006.
- Lugade AA, Moran JP, et al. Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol. 174:7516-23, 2005.
- Gerber, S. A., M. J. Turner, et al. Characterization of a lymph node within the mouse prostate: Detailed analysis using whole mount histology. Prostate 63: 105-16, 2005.
- Moran JP, Gerber SA, Martin CA, Frelinger JG, Lord EM. Transfection of the genes for interleukin-12 into the K1735 melanoma and the EMT6 mammary sarcoma murine cell lines reveals distinct mechanisms of antitumor activity. Int J Cancer. 106:690-8, 2003.
- Gerber SA, Moran JP, Frelinger JG, Frelinger JA, Fenton BM, Lord EM. "Mechanism of IL-12 mediated alterations in tumour blood vessel morphology: analysis using whole-tissue mounts." Br J Cancer 88:1453-61, 2003.
- Fisher TL, Nocera M, Willis RA, et al. Generation of monoclonal antibodies specific for human kallikrein 2 (hK2) using hK2-expressing tumors. Prostate 51:153-65, 2002.
- Turner MJ, Abdul-Alim CS, Willis RA, Fisher TL, Lord EM, Frelinger JG. "T-cell antigen discovery (T-CAD) assay: a novel technique for identifying T cell epitopes." J Immunol Methods. 256:107-19, 2001.
- Lord E, Paoni S. "Effects of radiation on tumor intravascular oxygenation, vascular configuration, development of hypoxia, and clonogenic survival." Radiat Res. 155:360-8, 2001.
- Brown DM, Fisher TL, Wei C, Frelinger JG, Lord EM. Tumours can act as adjuvants for humoral immunity. Immunology 102:486-97, 2001.
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