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Laboratory of Experimental Immunology

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Overview

The Laboratory of Experimental Immunology (LEI), together with the Laboratory of Molecular Immunoregulation (LMI), is part of the Cancer and Inflammation Program (CIP). The CIP constitutes the major immunologic component of the CCR's inflammation and cancer initiative, which spans the NCI's campuses in Frederick and Bethesda and seeks to partner NCI's expertise in inflammation and immunology with its cutting-edge cancer etiology and carcinogenesis program.

Recent studies are shedding a new light on how innate resistance, as an integral part of inflammation, and adaptive immunity participate in oncogenesis and tumor surveillance. For a long time, innate resistance was considered a primitive nonspecific form of resistance to infections that was eclipsed by the potent and specific acquired immunity of higher organisms. More recently, it has been recognized that innate resistance is not only the first line of defense against infections but also sets the stage and is necessary for the development of adaptive immunity. Advances in cancer biology now reveal that what used to be considered the defensive mechanisms of innate resistance and inflammation are indeed manifestations of tissue homeostasis and control of cellular proliferation that have many pleiotropic effects on carcinogenesis and tumor progression and dissemination. The interaction of the inflammatory mediators and effector cells with carcinogenesis and tumor progression is complicated and results in effects that either favor or impede tumor progression.

The investigators at the LEI conduct studies on basic mechanisms of innate resistance, inflammation, and adaptive immunity, their pharmacological modulation by biological response modifiers as well as the application of these studies to the understanding of the control of the carcinogenesis process and to cancer therapy/prevention. Basic science approaches utilize experimental animal studies as well as cellular, biochemical, and molecular techniques to study the regulation of cell-mediated immune effector mechanisms, cytokine gene expression and function, biochemistry of receptor-mediated signaling in leukocytes, and the biology of growth factors as they relate to cancer and other diseases. Based on cellular and molecular evaluation of biologicals, this information is then translated into immune modulation and immunotherapy protocols in experimental animals, and hypotheses suitable for testing in cancer patients are formulated.

The LEI is composed of 12 sections:

- The Molecular Immunology Section (Dr. Steve Anderson) investigates mechanisms controlling selective gene activation in the immune system, with an emphasis on receptors for class I MHC and the stochastic processes controlling activation of the human killer cell immunoglobulin-like receptor (KIR) and mouse Ly49 gene families.

- The HLA Immunogenetics Section (Dr. Mary Carrington) investigates the host genetic effects on human disease. The primary candidates include the HLA class I and II genes located within the human Major Histocompatibility Complex (MHC), because of their central role in the immune response.

- The Human Genetics Section (Dr. Michael Dean) conducts molecular genetic studies on cancer and other complex diseases. Using DNA sequencing of tumors, HGS scientists explore the molecular basis of cancer and the application of this knowledge to improved diagnosis and therapy.

- The Protein Interactions Section (Dr. Dimiter Dimitrov) focuses on development of human monoclonal antibodies including isolated engineered antibody domains for prevention and treatment of cancer and other diseases.

- The Inflammation and Tumorigenesis Section (Dr. Yinling Hu) studies the mechanism of lung and skin tumorigenesis, the effect of inflammatory microenvironments on the development of lung and skin squamous cell carcinomas, and the role of IKKalpha in the development of lymph cells and organs.

- The Immune Modulation Section (Dr. Dennis Klinman) studies immunostimulatory and immunosuppressive agents, their ability to alter the immune milieu, and their impact on the development of inflammatory and oncogenic processes.

- The Leukocyte Signaling Section (Dr. Daniel McVicar) dissects the signaling cascades of leukocyte regulatory receptors including the TREM, KIR, and Ly49s toward an understanding of the mechanisms underlying the innate immune system role in the development of, and subsequent response to, cancer.

- The Structural Bioinformatics Section (Dr. Ruth Nussinov) is focusing on the key role and principles of allostery under normal conditions, in disease and in allosteric drug discovery.

- The Molecular Immunotherapy Section (Dr. Thomas Sayers) studies the molecular amplification of apoptotic signaling in tumor cells by TNF family members, and assesses the modification of inflammation by metastatic cancer cells.

- The Cancer Immunobiology Section (Dr. Giorgio Trinchieri) studies the role of dendritic cells, other innate or adaptive effector cell types, and pro-inflammatory or immunoregulatory cytokines on infections, carcinogenesis and cancer therapy. The regulation of systemic inflammation by the commensal microbiota and its effect on viral and chemical carcinogenesis, genetic instability and response to anti-cancer therapy is presently a major focus of research.

- The Experimental Therapeutics Section (Dr. Robert Wiltrout) studies the cellular and molecular mechanisms by which cytokines regulate inflammation and host anti-tumor immune responses in the tumor and organ microenvironments, and performs preclinical trials using combinations of immunomodulatory cytokines in transplantable and oncogene-driven rodent tumor models.

- The Cellular and Molecular Immunology Section (Dr. Howard Young) studies the consequences of chronic cytokine gene expression in the host. A primary focus of research is on IFN-gamma, an important mediator of inflammation and the host immune response.

This page was last updated on 7/9/2014.