Immune Mechanisms Program
Harry D. Bear, M.D., Ph.D.
(804) 828-9325
hdbear@vcu.edu
Andrew C. Larner, M.D., Ph.D.
(804) 828-2903
alarner@vcu.edu
Although surgery, radiation therapy and chemotherapy constitute standard modalities to treat cancer patients, they often meet with limited success, thereby leading to significant mortality. The manipulation of the patient’s immune response to increase recognition of, and killing of, tumor cells offers an important and exciting modality for the treatment of cancer. To accomplish this, it is critical to understand the basic mechanisms involved in antigen processing and presentation, as well as activation of immune effector cells and their use in the treatment of cancer.
It has also become evident that intrinsically potent immune responses may not eradicate or control neoplasms, in large part because of a variety of escape mechanisms that either suppress the immune response or facilitate tumor cells’ evasion of immune attack. Tumor cells are known to evade the action of the immune system through a variety of mechanisms, including down-regulation of MHC molecules, lack of critical co-stimulatory molecules, production of immunosuppressive molecules and loss of relevant tumor antigens. Studies aimed at understanding these pathways will help in developing treatments that enable the immune cells to recognize and destroy the tumor cells in the setting of tumor vaccines or adoptive immunotherapy. Interestingly, cells of the immune system also undergo development of neoplasia at a high frequency. Furthermore, immune cells may serve as models for studying the signaling pathways involved in growth, differentiation and inflammation; understanding these processes may lead to development of novel strategies to prevent tumorigenesis.
The Immune Mechanisms Program focuses on basic and applied research in immunology aimed at understanding the mechanisms underlying the roles of immune cells in tumorigenesis and immune responses to cancer. These research themes are designed to lead to development of novel immunotherapeutic approaches for the treatment and prevention of cancer and also to improve existing modes of therapy. A subset of tumor immunologists in this Program is also investigating mechanisms of tumor escape from immune attack, such as antigen loss, decreased MHC expression and suppressor cells. The Program’s membership currently includes investigators from basic and clinical departments including the Departments of Microbiology and Immunology, Biochemistry and Molecular Biology, Surgery, Neurosurgery, Internal Medicine, Pediatrics, and Human Genetics in the School of Medicine, the Department of Biology in the College of Humanities and Sciences, and the Department of Adult Health Nursing in the School of Nursing.
Scientific objectives
There are two specific objectives:
- Understanding cellular and molecular mechanisms of regulation of immune cell growth and differentiation. In this aim, studies will be performed to delineate (a) the role of apoptosis in immune cell-tumor cell interactions, (b) cell signaling in normal and transformed T lymphocytes, B lymphocytes and other cells of the immune system and (c) the mechanisms by which chronic inflammation and immunosuppression contribute to neoplastic transformation.
- Analysis of anti-tumor immune effector mechanisms and tumor escape mechanisms, and development of immunotherapeutic approaches to cancer treatment. This aim includes studies on (a) vaccines and the role of T lymphocytes in anti-tumor immunity, (b) modifying immune responses to cancer to induce tumor regression and improve patient outcomes, and (c) understanding mechanisms that may contribute to tumor escape from immune attack. In the area of research education, Program members continue to hold two T32 training grants that support graduate students and postdoctoral fellows. The IM Program offers a highly interactive environment for the members and trainees to discuss and develop cutting-edge research strategies for more effective treatment of cancer.
Program goals
There are six overall goals:
- Facilitating intraprogrammatic collaborations that integrate the scientific focus of investigators in the basic and/or clinical areas of cancer immunology and immunotherapy. This is accomplished by juxtaposition of laboratory space in Massey, which is organized by programmatic interests, by sponsorship and organizational assistance with monthly IM Program meetings at which investigators present and discuss their research, and by providing “start-up” funding for collaborative projects.
- Fostering interprogrammatic projects that provide the basis for interdisciplinary research.
- Development of new and ongoing bench-to-bedside research in cancer immunologic therapy. This is encouraged through facilitating scientific exchange at IM Program meetings and in the multidisciplinary disease-specific meetings and by Cancer Center funding of the early phases of clinical translational studies.
- Promoting the growth and development of individual cancer immunology-related programs of junior faculty by providing mentorship, facilities and resources for interactions.
- Providing broad-based training to pre- and postdoctoral scholars, as well as professional students, in the field of tumor immunology and therapy.
- Encouraging high-risk pilot projects that offer significant impact on cancer research and treatment. The IM Program fosters an interactive environment by holding informal, small-group meetings, monthly Program meetings and an annual retreat.
