Photo of Harvey Cantor,  MD

Harvey Cantor, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute


harvey_cantor@dfci.harvard.edu

Harvey Cantor, MD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Baruj Benacerraf Professor of Microbiology and Immunobiology, Microbiology and Immunobiology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

The Cantor lab studies the development and function of T-cell subsets. Early studies indicated that the thymus gave rise to two major lineages of T cells that recognized the MHC class II and class I molecules and were equipped to mediate distinct immunological functions before overt encounter with antigen. These experiments were based on the idea that the pattern of proteins expressed on the cell-surface could be used to separate and define the developmental and functional components of the immune system. This approach was also used to dissect cell-mediated immunity into its cellular components and to isolate natural killer cells, and more recently, to define an inhibitory interaction between natural killer cells and autoreactive TH cells that has led to phase I clinical trials of an antibody that may target this interaction in RA patients.

Current studies in the Cantor lab have begun to define a lineage of CD8+ regulatory T cells (Treg) that inhibits the development of autoimmune disease and may regulate antitumor immunity. Recent studies have suggested that expression of the Helios transcription factor by Treg ensures a stable inhibitory phenotype and maintenance of self tolerance in the face of inflammatory and infectious challenge.

 

Publications

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  • Leavenworth JW, Verbinnen B, Wang Q, Shen E, Cantor H. Intracellular osteopontin regulates homeostasis and function of natural killer cells. Proc Natl Acad Sci U S A 2015; 112:494-9. PubMed
  • Alvarez Arias DA, Kim HJ, Zhou P, Holderried TA, Wang X, Dranoff G, Cantor H. Disruption of CD8+ Treg activity results in expansion of T follicular helper cells and enhanced antitumor immunity. Cancer Immunol Res 2014; 2:207-16. PubMed
  • Zhou P, Shaffer DR, Alvarez Arias DA, Nakazaki Y, Pos W, Torres AJ, Cremasco V, Dougan SK, Cowley GS, Elpek K, Brogdon J, Lamb J, Turley SJ, Ploegh HL, Root DE, Love JC, Dranoff G, Hacohen N, Cantor H, Wucherpfennig KW. In vivo discovery of immunotherapy targets in the tumour microenvironment. Nature 2014; 506:52-7. PubMed
  • Kim HJ, Cantor H. CD4 T-cell Subsets and Tumor Immunity: The Helpful and the Not-so-Helpful. Cancer Immunol Res 2014; 2:91-8. PubMed
  • Holderried TA, Lang PA, Kim HJ, Cantor H. Genetic disruption of CD8+ Treg activity enhances the immune response to viral infection. Proc Natl Acad Sci U S A 2013; 110:21089-94. PubMed
  • Kreslavsky T, Kim HJ, Koralov SB, Ghitza D, Buch T, Cantor H, Rajewsky K, von Boehmer H. Negative selection, not receptor editing, is a physiological response of autoreactive thymocytes. J Exp Med 2013; 210:1911-8. PubMed
  • Leavenworth JW, Tang X, Kim HJ, Wang X, Cantor H. Amelioration of arthritis through mobilization of peptide-specific CD8+ regulatory T cells. J Clin Invest 2013; 123:1382-9. PubMed
  • Kim HJ, Wang X, Radfar S, Sproule TJ, Roopenian DC, Cantor H. CD8+ T regulatory cells express the Ly49 Class I MHC receptor and are defective in autoimmune prone B6-Yaa mice. Proc Natl Acad Sci U S A 2011; 108:2010-5. PubMed
  • Kim HJ, Verbinnen B, Tang X, Lu L, Cantor H. Inhibition of follicular T-helper cells by CD8(+) regulatory T cells is essential for self tolerance. Nature 2010; 467:328-32. PubMed
  • Mitsdoerffer M, Lee Y, J├Ąger A, Kim HJ, Korn T, Kolls JK, Cantor H, Bettelli E, Kuchroo VK. Proinflammatory T helper type 17 cells are effective B-cell helpers. Proc Natl Acad Sci U S A 2010; 107:14292-7. PubMed
  • Varthaman A, Khallou-Laschet J, Clement M, Fornasa G, Kim HJ, Gaston AT, Dussiot M, Caligiuri G, Herbelin A, Kaveri S, Cantor H, Nicoletti A. Control of T cell reactivation by regulatory Qa-1-restricted CD8+ T cells. J Immunol 2010; 184:6585-91. PubMed
  • Arias DA, McCarty N, Lu L, Maldonado RA, Shinohara ML, Cantor H. Unexpected role of clathrin adaptor AP-1 in MHC-dependent positive selection of T cells. Proc Natl Acad Sci U S A 2010; 107:2556-61. PubMed
  • Leavenworth JW, Schellack C, Kim HJ, Lu L, Spee P, Cantor H. Analysis of the cellular mechanism underlying inhibition of EAE after treatment with anti-NKG2A F(ab')2. Proc Natl Acad Sci U S A 2010; 107:2562-7. PubMed
  • Egli D, Sandler VM, Shinohara ML, Cantor H, Eggan K. Reprogramming after chromosome transfer into mouse blastomeres. Curr Biol 2009; 19:1403-9. PubMed
  • Cornejo MG,Kharas MG,Werneck MB,Le Bras S,Moore SA,Ball B,Beylot-Barry M,Rodig SJ,Aster JC,Lee BH,Cantor H,Merlio JP,Gilliland DG,Mercher T. Constitutive JAK3 activation induces lymphoproliferative syndromes in murine bone marrow transplantation models. Blood 2009; 113:2746-54. PubMed
  • Cantor H,Shinohara ML. Regulation of T-helper-cell lineage development by osteopontin: the inside story. Nat Rev Immunol 2008; 9:137-41. PubMed
  • Lu L,Kim HJ,Werneck MB,Cantor H. 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 U S A 2008; 105:19420-5. PubMed
  • Lu L,Cantor H. Generation and regulation of CD8(+) regulatory T cells. Cell Mol Immunol 2009; 5:401-6. PubMed
  • Shinohara ML,Kim JH,Garcia VA,Cantor H. Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: role of intracellular osteopontin. Immunity 2008; 29:68-78. PubMed
  • Werneck MB,Lugo-Villarino G,Hwang ES,Cantor H,Glimcher LH. T-bet plays a key role in NK-mediated control of melanoma metastatic disease. J Immunol 2008; 180:8004-10. PubMed
  • Shinohara ML,Kim HJ,Kim JH,Garcia VA,Cantor H. Alternative translation of osteopontin generates intracellular and secreted isoforms that mediate distinct biological activities in dendritic cells. Proc Natl Acad Sci U S A 2008; 105:7235-9. PubMed
  • Colmenero P, Zhang AL, Qian T, Lu L, Cantor H, Soderstrom K, Engleman EG. Qa-1(b)-dependent modulation of dendritic cell and NK cell cross-talk in vivo. J Immunol 2007; 179:4608-15. PubMed
  • Lu L, Ikizawa K, Hu D, Werneck MB, Wucherpfennig KW, Cantor H. Regulation of Activated CD4(+) T Cells by NK Cells via the Qa-1-NKG2A Inhibitory Pathway. Immunity 2007; 26:593-604. PubMed
  • Shinohara ML, Lu L, Bu J, Werneck MB, Kobayashi KS, Glimcher LH, Cantor H. Osteopontin expression is essential for interferon-alpha production by plasmacytoid dendritic cells. Nat Immunol 2006; 7:498-506. PubMed
  • Shinohara ML, Jansson M, Hwang ES, Werneck MB, Glimcher LH, Cantor H. T-bet-dependent expression of osteopontin contributes to T cell polarization. Proc Natl Acad Sci U S A 2005; 102:17101-6. PubMed
  • Paust S, Cantor H. Regulatory T cells and autoimmune disease. Immunol Rev 2005; 204:195-207. PubMed
  • McCarty N, Paust S, Ikizawa K, Dan I, Li X, Cantor H. Signaling by the kinase MINK is essential in the negative selection of autoreactive thymocytes. Nat Immunol 2004; 6:65-72. PubMed
  • Bach JF, Bendelac A, Brenner MB, Cantor H, De Libero G, Kronenberg M, Lanier LL, Raulet DH, Shlomchik MJ, von Herrath MG. The role of innate immunity in autoimmunity. J Exp Med 2004; 200:1527-31. PubMed
  • Sarantopoulos S, Lu L, Cantor H. Qa-1 restriction of CD8+ suppressor T cells. J Clin Invest 2004; 114:1218-21. PubMed
  • Paust S, Lu L, McCarty N, Cantor H. Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease. Proc Natl Acad Sci U S A 2004; 101:10398-403. PubMed
  • McCarty N, Shinohara ML, Lu L, Cantor H. Detailed analysis of gene expression during development of T cell lineages in the thymus. Proc Natl Acad Sci U S A 2004; 101:9339-44. PubMed
  • 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. PubMed
  • Panoutsakopoulou V, Huster KM, McCarty N, Feinberg E, Wang R, Wucherpfennig KW, Cantor H. Suppression of autoimmune disease after vaccination with autoreactive T cells that express Qa-1 peptide complexes. J Clin Invest 2004; 113:1218-24. PubMed
  • Cantor H. Reviving suppression? Nat Immunol 2004; 5:347-9. PubMed
  • Kissler S, Lu L, Cantor H. Thymic selection can compensate for mutations affecting T cell activation and generate a normal T cell repertoire in mutant mice. Proc Natl Acad Sci U S A 2003; 101:210-4. PubMed
  • Ye Q, Press B, Kissler S, Yang XF, Lu L, Bassing CH, Sleckman BP, Jansson M, Panoutsakopoulou V, Trimble LA, Alt FW, Cantor H. T cell costimulation through CD28 depends on induction of the Bcl-xgamma isoform: analysis of Bcl-xgamma-deficient mice. J Exp Med 2002; 196:87-95. PubMed
  • Trimble LA, Prince KA, Pestano GA, Daley J, Cantor H. Fas-dependent elimination of nonselected CD8 cells and lpr disease. J Immunol 2002; 168:4960-7. PubMed
  • Huster KM, Panoutsakopoulou V, Prince K, Sanchirico ME, Cantor H. T cell-dependent and -independent pathways to tissue destruction following herpes simplex virus-1 infection. Eur J Immunol 2002; 32:1414-9. PubMed
  • Weber GF, Bronson RT, Ilagan J, Cantor H, Schmits R, Mak TW. Absence of the CD44 gene prevents sarcoma metastasis. Cancer Res 2002; 62:2281-6. PubMed
  • Jansson M, Panoutsakopoulou V, Baker J, Klein L, Cantor H. Cutting edge: Attenuated experimental autoimmune encephalomyelitis in eta-1/osteopontin-deficient mice. J Immunol 2002; 168:2096-9. PubMed
  • Panoutsakopoulou V, Sanchirico ME, Huster KM, Jansson M, Granucci F, Shim DJ, Wucherpfennig KW, Cantor H. Analysis of the relationship between viral infection and autoimmune disease. Immunity 2001; 15:137-47. PubMed
  • Lu L, Ikizawa K, Hu D, Werneck MBF, Wucherpfennig KW, Cantor H. Regulation of activated CD4+ T cells by NK cells via the Qa-1-NKG2A inhibitory pathway. Immunity 2008; 26:593-604.
  • Pestano GA, Zhou Y, Trimble LA, Daley J, Weber GF, Cantor H. Inactivation of misselected CD8 T cells by CD8 gene methylation and cell death. Science 1999; 284:1187-91. PubMed
  • Zhao ZS, Granucci F, Yeh L, Schaffer PA, Cantor H. Molecular mimicry by herpes simplex virus-type 1: autoimmune disease after viral infection. Science 1998; 279:1344-7. PubMed
  • Noble A, Pestano GA, Cantor H. Suppression of immune responses by CD8 cells. I. Superantigen-activated CD8 cells induce unidirectional Fas-mediated apoptosis of antigen-activated CD4 cells. J Immunol 1998; 160:559-65. PubMed
  • Yang XF, Weber GF, Cantor H. A novel Bcl-x isoform connected to the T cell receptor regulates apoptosis in T cells. Immunity 1997; 7:629-39. PubMed
  • Weber GF, Ashkar S, Glimcher MJ, Cantor H. Receptor-ligand interaction between CD44 and osteopontin (Eta-1). Science 1996; 271:509-12. PubMed
  • Avery AC, Zhao ZS, Rodriguez A, Bikoff EK, Soheilian M, Foster CS, Cantor H. Resistance to herpes stromal keratitis conferred by an IgG2a-derived peptide. Nature 1995; 376:431-4. PubMed
  • Weber GF, Abromson-Leeman S, Cantor H. A signaling pathway coupled to T cell receptor ligation by MMTV superantigen leading to transient activation and programmed cell death. Immunity 1995; 2:363-72. PubMed
  • Weber GF, Cantor H. Phosphatidylinositol synthesis is a proximal event in intracellular signaling coupled to T cell receptor ligation. Differential induction by conventional antigen and retroviral superantigen. J Immunol 1994; 152:4433-43. PubMed
  • Crump AL, Grusby MJ, Glimcher LH, Cantor H. Thymocyte development in major histocompatibility complex-deficient mice: evidence for stochastic commitment to the CD4 and CD8 lineages. Proc Natl Acad Sci U S A 1993; 90:10739-43. PubMed
  • Liu H, Lampe MA, Iregui MV, Cantor H. Clonal unresponsiveness results from an interaction between staphylococcal enterotoxin B and T cells expressing unexpected V beta elements. Int Immunol 1992; 4:851-9. PubMed
  • Lampe MA, Patarca R, Iregui MV, Cantor H. Polyclonal B cell activation by the Eta-1 cytokine and the development of systemic autoimmune disease. J Immunol 1991; 147:2902-6. PubMed
  • Liu H, Lampe MA, Iregui MV, Cantor H. Conventional antigen and superantigen may be coupled to distinct and cooperative T-cell activation pathways. Proc Natl Acad Sci U S A 1991; 88:8705-9. PubMed
  • Patarca R, Wei FY, Iregui MV, Cantor H. Differential induction of interferon gamma gene expression after activation of CD4+ T cells by conventional antigen and Mls superantigen. Proc Natl Acad Sci U S A 1991; 88:2736-9. PubMed
  • Patarca R, Wei FY, Singh P, Morasso MI, Cantor H. Dysregulated expression of the T cell cytokine Eta-1 in CD4-8- lymphocytes during the development of murine autoimmune disease. J Exp Med 1990; 172:1177-83. PubMed
  • Singh RP, Patarca R, Schwartz J, Singh P, Cantor H. Definition of a specific interaction between the early T lymphocyte activation 1 (Eta-1) protein and murine macrophages in vitro and its effect upon macrophages in vivo. J Exp Med 1990; 171:1931-42. PubMed
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