Dr. Laszlo Radvanyi
The University of Texas MD Anderson Cancer Center
Department of Melanoma Medical Oncology
- Tumor immunology
- Cancer vaccine development
- Adoptive T-cell therapy
- Antigen discovery and characterization for immunotherapy of cancer
My laboratory is located in the new Center for Cancer Immunology (CCIR) at the South Campus of MD Anderson Cancer Center (MDACC). My research focuses on human immunology by addressing both and basic and clinical research questions on the role of human T cells in anti-tumor immune responses. We take an interdisciplinary approach by working together with a team of basic and clinical researchers. We have two main research areas in the lab. The first area we are studying is the biology of tumor-infiltrating lymphocytes (TIL) from cancer patients and their phenotypic and functional characterization. These cells are isolated and cultured from surgical tumor specimens. The key questions we are addressing are how different T-cell subsets isolated from tumors further proliferate and differentiate when re-stimulated with tumor antigens and how different cytokines and cell signaling molecules called "costimulatory molecules" affect their proliferation and effector function. We are particularly interested in the tumor necrosis factor receptor (TNF-R) family of receptors on activated T cells and how they regulate TIL survival and function. Recently, we have discovered a novel population of abnormally-differentiated T cells residing in tumors that we are studying presently. Flow cytometry is extensively used to characterize isolated T cells that are sorted into different subsets and cultured to study their individual functional properties. We are also studying a unique group of T-cell immunoregulatory molecules in cancer called "negative costimulatory B7 molecules" that we have found expressed on melanoma and other types of cancer cells. A key question we are addressing is whether these B7 molecules activate suppressive regulatory CD4+ T cells, also called "Tregs", in cancer that shut-off anti-tumor CD8+ T-cell (killer cell) responses. We are characterizing the functional changes in different subsets of these Tregs in cancer patients undergoing different forms of therapy. The second major area of interest in the lab is in breast cancer. In a recent gene expression screen we found a novel transcription factor called "TRPS-1" to be over-expressed in a high percentage of human breast cancer specimens, especially in the most common form of breast cancer expressing the estrogen receptor and dependent on estrogen for growth and survival. We are characterizing the expression and function of this new transcription factor in breast cancer and how it regulates estrogen signaling. This project is done in collaboration with members of the Breast Medical Oncology Department at MDACC (Dr. Radvanyi has a cross-appointment to this department).
Students in the lab will gain comprehensive theoretical and technical knowledge in human tumor immunology and using mouse tumor models, particularly human xenograft models. A number of cellular immunology tools are used in the lab, including multi-color flow cytometry to phenotypically characterize T-cell populations and perform intracellular staining, enzyme-linked immunospot (ELISPOT) assays, enzyme-linked immunoserological (ELISA) assays, multiplex cytokine analysis (Luminex system), T-cell proliferation and cytotoxic T-cell assays, T-cell receptor (TCR) staining using tetramers, TCR clonotype analysis, telomere length analysis, and immunohistochemistry. We use primary-cultured human T cells and antigen-presenting cells such as dendritic cells isolated from tumors and peripheral blood from normal donors and cancer patients to characterize anti-tumor immune responses. Students will also be exposed to a number of molecular biology tools, including generation of recombinant protein antigens, expression of proteins and signaling modulators in lentivirus/adenovirus and retrovirus systems, and gene knockdown technologies. Discoveries in the lab are translated into the clinic in novel forms of immunotherapy for cancer in collaboration with clinicians at MDACC. Thus, students will also have the opportunity to be directly exposed to how bench research is translated into the clinic on a regular basis.
Program in Immunology