Jelena Levitskaya, MD
Center & Institute Affiliation(s):
I focus my research on the mechanisms of immunoediting and immune escape of malignant and pathogen-infected cells Induction of apoptosis in virus-infected or tumor cells by cytotoxic T cells (CTLs) is mediated by at least two mechanisms: granule-mediated exocytosis of cytolytic molecules and triggering of death receptors expressed on the surface of target cells. Secreted and surface associated molecules expressed by CTLs and involved in triggering death of target cells are referred to as effector molecules. In the course of tumor development and progression, immunological effector molecules can mediate multiple and sometimes opposing effects such as (i) induction of tumor cell death; (ii) enhancement of tumor immunogeneicity or/and antigeneicity; (iii) immunoediting of cancer leading to tumor immune escape, and (iiii) promotion of tumor growth. My current research interests include analysis of various effects exerted by the immune system on human tumor cells. In our work, we are aiming at: (I) Identification of signals modulating the MHC class I antigen presentation in tumor and pathogen infected cells; (II) Description of mechanism(s) leading to the reduced susceptibility of tumors to cytotoxic T lymphocyte (CTL)-mediated killing induced via granule exocytosis and death receptors; (III) Dissection of non-apoptotic signaling pathways transduced via surface death receptors in the regulation of tumor growth.
Topics of current research in tumor immunology
1. Mechanisms of target cell resistance to perforin/granzyme mediated killing 2. Caspase-independent control of tumor cells by bystander immune activation 3. Autocrine TNF signaling as a target in cancer therapy
Topics of current research in infectious immunity
1. Immune modulation of host cells at the early stages of malaria infection. 2. Role of malaria infection in the pathogenesis of B cell malignancies.
For detailed description of current projects visit my home page
Tumor immunology, Infectious immunity, Antigen presentation, Immunogeneicity, cytotoxic T lymphocytes (CTLs), Immunoediting, Immune escape, Autocrine TNF signaling, Bystander immune activation, Immune escape of malaria parasite, Burkitt’s lymphoma, Uveal melanoma, Neuroblastoma
1. Hallermalm K, Seki K, De Geer A, Motyka B, Bleackley CR, Jager M, Froelich, Kiessling R, Levitsky V and Jelena Levitskaya. Modulation of the tumor cell phenotype by interferon-gamma results in resistance of uveal melanoma cells to granule-mediated lysis by cytotoxic lymphocytes. J Immunology. 2008. Mar15;180(6):3766-74
2. Carlson LM, De Geer A, Kogner P. and Levitskaya Jelena. Differentiation induced by physiological and pharmacological stimuli leads to increased antigenicity of human neuroblastoma cells. Cell Research. 2008 Mar;18(3):398-411.
3. De Geer A., Carlson LM, Kogner P. and Levitskaya Jelena. Soluble factors released by activated cytotoxic T lymphocytes interfere with death receptor pathways in neuroblastoma. Cancer Immunol Immunother. 2007. Oct 26.
4. Vertuani S, Dubrovska E, Levitsky V, Jager MJ, Kiessling R and Jelena Levitskaya. Retinoic acid elicits cytostatic, cytotoxic and immunomodulatory effects on uveal melanoma cells. Cancer Immunol Immunother. 2007, Feb; 56(2):193-204.
5. Anna De Geer, Rolf Kiessling, Victor Levitsky and Jelena Levitskaya. Cytotoxic T lymphocytes Induce Caspase-Dependent and -Independent Cell Death in Neuroblastomas in a MHC-Non-Restricted Fashion. J. Immunology. 2006 Dec 1;177(11):7540-50