• Researcher Profile

    Harvey Cantor, MD

     
    Yawkey Center for Cancer Care
     
    Chair, Department of Cancer Immunology & AIDS

    Baruj Benacerraf Professor of Microbiology and Immunobiology, Harvard Medical School

    Office phone: 617-632-3348
    Fax: 617-632-4630
    Email: harvey_cantor@dfci.harvard.edu

    Preferred contact method: email
     
     

    Research Department

    Cancer Immunology and AIDS

    Area of Research

    Development and function of T cells in the immune system and their distinctive markers that recognize different classes of MHC molecules, and perform three major functions: T cell help, T cell inflammation, and T cell killing.

    Dana-Farber Cancer Institute
    450 Brookline Avenue
    Smith 722
    Boston, MA 02215

    Biography

    After receiving an MD from New York University in 1967, Dr. Cantor trained at the National Institutes of Health and National Institute for Medical Research in London. After a residency in medicine at Stanford, he joined the DFCI and Harvard faculty in 1974; since 1997, he has chaired the Department of Cancer Immunology and AIDS. He directed the DF/HCC Program in Cancer Immunology and now serves on its Steering Committee. He engages in teaching/training within the Harvard Medical School Graduate Program in Immunology and directs NIH postdoctoral training programs in AIDS research and cancer immunology.

    Recent Awards

    • Member, American Academy of Arts & Sciences, 2010-
    • Fellow in Medical Sciences, American Association for the Advancement of Science, 2005-
    • Clontech Lecture, Indiana University, 2005
    • Crano Memorial Lecture, University of Pittsburgh, 2003
    • Member, National Academy of Sciences, 2002-
    • Gershon Memorial Lecture, Yale University, 2002

    Research

    Development and function of T cells in the immune system and their distinctive markers that recognize different classes of MHC molecules, and perform three major functions: T cell help, T cell inflammation, and T cell killing.

    The focus of the lab is on the contribution of T cell subsets to the maintenance of protective immunity and prevention of autoimmune disease. Our studies of T cell development in the thymus have defined a new kinase (MINK) that is activated after engagement of the TCR and self peptides that initiates a pathway culminating in cellular apoptosis (negative selection) (McCarty et al., 2005).

    A comprehensive understanding of complex biological information systems, including the immune system and nervous system, requires definition of cells that are genetically programmed to suppress signal transmission and inhibit cellular responses (Hu et al., 2004; Lu et al., 2008). Analysis of the immune system has defined a sublineage of CD4+ T cells, termed CD4+ Treg, that can inhibit excessive inflammatory immune responses. However, regulatory T cells that are genetically programmed to inhibit development of autoantibody formation and SLE-like disease have not been defined.

    After stimulation by class I MHCpeptide complexes, the majority of CD8+ T cells differentiate into memory and effector cells that secrete cytokines and lyse target cells recognized as foreign. We have defined a subset of CD8+ T cells (CD8+ Treg) that prevents autoantibody formation and maintains self tolerance, an essential feature of the adaptive immune system (Kim et al., 2010). Identification of a suppressive sublineage of CD8 T cells essential to prevent the generation of pathogenic autoantibody production and to ensure self tolerance has fundamental relevance to understanding the immune system and suggests new approaches to the treatment of SLE and other autoimmune disorders.

    More recent studies have shown that NK cells also contribute to the control of adaptive immune responses and that this pathway is also regulated by Qa-1 (Lu et al., 2007). These studies have extended the functional reach of the NK system to include regulation of adaptive T cell responses and suggest a new clinical strategy for elimination of autoreactive T cells that drive autoimmune disorders, including SLE.

    Finally, studies of the differentiation of T-helper cells have defined an interaction between dendritic cells and T cells that regulates the development of Th1 cells and Th17 cells (Shinohara et al., 2005; Shinohara et al., 2006; Shinohara et al., 2008). Elaboration of the cytokines Osteopontin and IFN promotes the Th1 response and suppresses the Th17 response, establishing the pattern of T-helper cell differentiation displayed during the large majority of immune responses.

    Select Publications

    • McCarty N, Paust S, Ikizawa K, Dan I, Li X, Cantor H. Signaling by MINK plays an essential role in negative selection of autoreactive thymocytes. Nat Immunol 2005;6:65-72.
    • Hu D, Ikizawa K, Lu L, Sanchirico ME, Shinohara ML, Cantor H. Analysis of regulatory CD8 T cells in Qa-1-deficient mice. Nat Immunol 2004;5:516-23.
    • Shinohara ML, Kim J-H, Garcia VA, Cantor H. 2008. Engagement of the Type I interferon receptor on dendtritic cells inhibits promotion of Th17 cells: central role of intracellular Osteopontin. Immunity 29: 68-78.
    • Lu L, Kim H-J, Werneck MBF, Cantor H. 2008. Regulation of CD8+ regulatory T cells: Interruption of the NKG2A-Qa-1 interaction allows robust suppressive activity and resolution of autoimmune disease. Proc Natl Acad Sci USA 105:19420-5.
    • Lu L, Ikizawa K, Hu D, Werneck MBF, Wucherpfennig KW, Cantor H. 2007. Regulation of activated CD4+ T cells by NK cells via the Qa-1-NKG2A inhibitory pathway. Immunity, 26:593-604.
    • *Alvarez Arias DA, *McCarty N, Lu L, Maldonado RA, Shinohara ML, and Cantor H. 2010. Unexpected role of clathrin adaptor AP-1 in MHC-dependent positive selection of T cells. Proc. Natl. Acad. Sci. USA, 107:2556-2561.
    • *Leavenworth JW, *Schellack C, *Kim H-J, Lu L, Spee P, and Cantor H. 2010 Analysis of the cellular mechanism underlying inhibition of EAE after treatment with anti-NKG2A F(ab)′2. Proc. Natl. Acad. Sci. USA, 107:2562-2567.
    • Kim H-J, Verbinnen B, Tang X, Lu L and Cantor H. 2010. Inhibition of follicular T helper cells by CD8+ Treg is essential for self tolerance. Nature , in press.

    Trainees

    • Kim, Hye-Jung, PhD
    • Tang, Xiaolei, MD, PhD
    • Alvarez Arias, Diana A, PhD
    • Kadakia, Tejas, PhD
    • Chen, Xiaochun, PhD
    • Leavenworth, Jianmei W., PhD
    • Radfar, Soroosh, PhD