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, Division of Immunology , 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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  • Nakagawa H, Sido JM, Reyes EE, Kiers V, Cantor H, Kim HJ. Instability of Helios-deficient Tregs is associated with conversion to a T-effector phenotype and enhanced antitumor immunity. Proc Natl Acad Sci U S A 2016; 113:6248-53. PubMed
  • Yin J, Leavenworth JW, Li Y, Luo Q, Xie H, Liu X, Huang S, Yan H, Fu Z, Zhang LY, Zhang L, Hao J, Wu X, Deng X, Roberts CW, Orkin SH, Cantor H, Wang X. Ezh2 regulates differentiation and function of natural killer cells through histone methyltransferase activity. Proc Natl Acad Sci U S A 2015. PubMed
  • Kim HJ, Barnitz RA, Kreslavsky T, Brown FD, Moffett H, Lemieux ME, Kaygusuz Y, Meissner T, Holderried TA, Chan S, Kastner P, Haining WN, Cantor H. Stable inhibitory activity of regulatory T cells requires the transcription factor Helios. Science 2015; 350:334-9. PubMed
  • 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
  • Leavenworth JW, Verbinnen B, Yin J, Huang H, Cantor H. A p85α-osteopontin axis couples the receptor ICOS to sustained Bcl-6 expression by follicular helper and regulatory T cells. Nat Immunol 2014; 16:96-106. PubMed
  • Kim HJ, Cantor H. The path to reactivation of antitumor immunity and checkpoint immunotherapy. Cancer Immunol Res 2014; 2:926-36. 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
  • 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, Jäger 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
  • 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
  • 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
  • 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
  • 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
  • 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
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