DF/HCC Program Affiliation

Cancer Immunology
Cancer Imaging

Lab Website

Pittet Lab

Research Abstract

My laboratory studies responses mediated by innate and adaptive immune cells. We look at how these cells interplay, respond to stimuli and exhibit regulatory or effector functions. Because in vitro readouts do not always recapitulate the complexity of in vivo environments, the discovery effort utilizes noninvasive, three-dimensional bioimaging technologies combined with novel cell trackers and molecular sensors. The modalities provide either real-time microscopic cellular resolution, quantitative whole organ information and/or have translational potential. Our goals are to develop approaches for comprehensive investigation of cell types in defined microenvironments, and to quantify and model information obtained by bioimaging. As detailed below, we have focused our efforts on the study of adaptive immune responses mediated by T cells, and innate immune responses mediated by mononuclear phagocytes. ADAPTIVE IMMUNE CELLS. T cells are specialized to recognize cells infected with intracellular pathogens or transformed cells expressing tumor-associated antigens. Cytotoxic T cells (CTL) execute their effector functions during direct physical interactions with their targets, which include release of lytic granules and secretion of cytokines. In contrast other T cells such as T regulatory (Treg) cells mediate dominant suppressive functions and can prevent the activity of CTL and other effector cells. Our understanding of how immune functions are regulated and integrated in vivo at the cellular level is, to a large extent, still speculative. We are studying how Treg cells repress CTL responses in vivo, and whether Treg cell-mediated tolerance can be reversed in therapy. INNATE IMMUNE CELLS. Mononuclear phagocytes exert crucial functions as scavengers and can trigger or regulate immune responses. Recent studies indicate that monocytes - the precursors of macrophages and dendritic cells - comprise separate subsets that 'commit' to specific functions. The activity of these subsets in vivo is largely unknown. We are studying tissue tropism, cellular differentiation and role in immunity of monocyte subsets in various inflammatory conditions. We are also testing whether these cells are potential targets in therapy.

Publications

• Nahrendorf M, Waterman P, Thurber G, Groves K, Rajopadhye M, Panizzi P, Marinelli B, Aikawa E, Pittet MJ, Swirski FK, Weissleder R.Hybrid in vivo FMT-CT imaging of protease activity in atherosclerosis with customized nanosensors.Arterioscler Thromb Vasc B
  19608968
• Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo V, Panizzi P, Figueiredo JL, Kohler RH, Chudnovskiy A, Waterman P, Aikawa E, Mempel TR, Libby P, Weissleder R, Pittet MJ.Identification of splenic reservoir monocytes and their deployment
  19644120
• Wildgruber M,Lee H,Chudnovskiy A,Yoon TJ,Etzrodt M,Pittet MJ,Nahrendorf M,Croce K,Libby P,Weissleder R,Swirski FK.Monocyte subset dynamics in human atherosclerosis can be profiled with magnetic nano-sensors.PLoS ONE 2009;4(5):e5663.
  19461894
• Leimgruber A,Berger C,Cortez-Retamozo V,Etzrodt M,Newton AP,Waterman P,Figueiredo JL,Kohler RH,Elpek N,Mempel TR,Swirski FK,Nahrendorf M,Weissleder R,Pittet MJ.Behavior of endogenous tumor-associated macrophages assessed in vivo using a functionalized nan
  19412430
• Swirski FK,Weissleder R,Pittet MJ.Heterogeneous In Vivo Behavior of Monocyte Subsets in Atherosclerosis.Arterioscler Thromb Vasc Biol 2009 Apr 16.
  19372462
• Pittet MJ.Behavior of immune players in the tumor microenvironment.Curr Opin Oncol 2009 Jan;21(1):53-9.
  19125019
• Cortez-Retamozo V,Swirski FK,Waterman P,Yuan H,Figueiredo JL,Newton AP,Upadhyay R,Vinegoni C,Kohler R,Blois J,Smith A,Nahrendorf M,Josephson L,Weissleder R,Pittet MJ.Real-time assessment of inflammation and treatment response in a mouse model of allergic
  19033674
• Cortez-Retamozo V,Swirski FK,Waterman P,Yuan H,Figueiredo JL,Newton AP,Upadhyay R,Vinegoni C,Kohler R,Blois J,Smith A,Nahrendorf M,Josephson L,Weissleder R,Pittet MJ.Real-time assessment of inflammation and treatment response in a mouse model of allergic
  18989378
• Libby P,Nahrendorf M,Pittet MJ,Swirski FK.Diversity of denizens of the atherosclerotic plaque: not all monocytes are created equal.Circulation 2008 Jun 24;117(25):3168-70.
  18574058
• Shaw SY,Westly EC,Pittet MJ,Subramanian A,Schreiber SL,Weissleder R.Perturbational profiling of nanomaterial biologic activity.Proc Natl Acad Sci U S A 2008 May 27;105(21):7387-92.
  18492802
• Magnusson FC,Liblau RS,von Boehmer H,Pittet MJ,Lee JW,Turley SJ,Khazaie K.Direct presentation of antigen by lymph node stromal cells protects against CD8 T-cell-mediated intestinal autoimmunity.Gastroenterology 2008 Apr;134(4):1028-37.
  18395084
• Weissleder R, Pittet MJ.Imaging in the era of molecular oncology.Nature 2008 Apr 3;452(7187):580-9.
  18385732
• Pittet MJ, Mempel TR.Regulation of T-cell migration and effector functions: insights from in vivo imaging studies.Immunol Rev 2008 Feb;221:107-29.
  18275478
• Nahrendorf M, Swirski FK, Aikawa E, Stangenberg L, Wurdinger T, Figueiredo JL, Libby P, Weissleder R, Pittet MJ.The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions.J Exp Med 2007 Nov 26;204(12):303
  18025128
• Swirski FK, Berger CR, Figueiredo JL, Mempel TR, von Andrian UH, Pittet MJ, Weissleder R.A near-infrared cell tracker reagent for multiscopic in vivo imaging and quantification of leukocyte immune responses.PLoS ONE 2007;2(10):e1075.
  17957257
• Tam JM, Upadhyay R, Pittet MJ, Weissleder R, Mahmood U.Improved in vivo whole-animal detection limits of green fluorescent protein-expressing tumor lines by spectral fluorescence imaging.Mol Imaging 2007 Jul-Aug;6(4):269-76.
  17711782
• Pittet MJ, Grimm J, Berger CR, Tamura T, Wojtkiewicz G, Nahrendorf M, Romero P, Swirski FK, Weissleder R.In vivo imaging of T cell delivery to tumors after adoptive transfer therapy.Proc Natl Acad Sci U S A 2007 Jul 24;104(30):12457-61.
  17640914
• Pittet MJ, Swirski FK, Reynolds F, Josephson L, Weissleder R.Labeling of immune cells for in vivo imaging using magnetofluorescent nanoparticles.Nat Protoc 2006;1(1):73-9.
  17406214
• Nahrendorf M, Sosnovik DE, Waterman P, Swirski FK, Pande AN, Aikawa E, Figueiredo JL, Pittet MJ, Weissleder R.Dual channel optical tomographic imaging of leukocyte recruitment and protease activity in the healing myocardial infarct.Circ Res 2007 Apr 27;10
  17379832
• Romero P, Zippelius A, Kurth I, Pittet MJ, Touvrey C, Iancu EM, Corthesy P, Devevre E, Speiser DE, Rufer N.Four functionally distinct populations of human effector-memory CD8+ T lymphocytes.J Immunol 2007 Apr 1;178(7):4112-9.
  17371966
• Swirski FK, Libby P, Aikawa E, Alcaide P, Luscinskas FW, Weissleder R, Pittet MJ.Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata.J Clin Invest 2007 Jan;117(1):195-205.
  17200719
• Mempel TR, Pittet MJ, Khazaie K, Weninger W, Weissleder R, von Boehmer H, von Andrian UH.Regulatory T cells reversibly suppress cytotoxic T cell function independent of effector differentiation.Immunity 2006 Jul;25(1):129-41.
  16860762
• Swirski FK, Pittet MJ, Kircher MF, Aikawa E, Jaffer FA, Libby P, Weissleder R.Monocyte accumulation in mouse atherogenesis is progressive and proportional to extent of disease.Proc Natl Acad Sci U S A 2006 Jul 5;103(27):10340-5.
  16801531
• Tréhin R, Figueiredo JL, Pittet MJ, Weissleder R, Josephson L, Mahmood U.Fluorescent nanoparticle uptake for brain tumor visualization.Neoplasia 2006 Apr;8(4):302-11.
  16756722
• Pittet MJ, Gati A, Le Gal FA, Bioley G, Guillaume P, de Smedt M, Plum J, Speiser DE, Cerottini JC, Dietrich PY, Romero P, Zippelius A.Ex vivo characterization of allo-MHC-restricted T cells specific for a single MHC-peptide complex.J Immunol 2006 Feb 15;1
  16455990
• Chen ML, Pittet MJ, Gorelik L, Flavell RA, Weissleder R, von Boehmer H, Khazaie K.Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo.Proc Natl Acad Sci U S A 2005 Jan 11;102(2):419-24.
  15623559
• Liénard D, Rimoldi D, Marchand M, Dietrich PY, van Baren N, Geldhof C, Batard P, Guillaume P, Ayyoub M, Pittet MJ, Zippelius A, Fleischhauer K, Lejeune F, Cerottini JC, Romero P, Speiser DE.Ex vivo detectable activation of Melan-A-specific T cells correla
  15149168
• Zippelius A, Batard P, Rubio-Godoy V, Bioley G, Liénard D, Lejeune F, Rimoldi D, Guillaume P, Meidenbauer N, Mackensen A, Rufer N, Lubenow N, Speiser D, Cerottini JC, Romero P, Pittet MJ.Effector function of human tumor-specific CD8 T cells in melanoma le
  15087405
• Movassagh M, Spatz A, Davoust J, Lebecque S, Romero P, Pittet M, Rimoldi D, Liénard D, Gugerli O, Ferradini L, Robert C, Avril MF, Zitvogel L, Angevin E.Selective accumulation of mature DC-Lamp+ dendritic cells in tumor sites is associated with efficient
  15026362
• Speiser DE, Pittet MJ, Rimoldi D, Guillaume P, Luescher IF, Liénard D, Lejeune F, Cerottini JC, Romero P.Evaluation of melanoma vaccines with molecularly defined antigens by ex vivo monitoring of tumor-specific T cells.Semin Cancer Biol 2003 Dec;13(6):461
  15001165
• Zippelius A, Bioley G, Le Gal FA, Rufer N, Brandes M, Batard P, De Smedt M, Plum J, Speiser DE, Cerottini JC, Dietrich PY, Romero P, Pittet MJ.Human thymus exports naive CD8 T cells that can home to nonlymphoid tissues.J Immunol 2004 Mar 1;172(5):2773-7.
  14978076
• Pittet MJ, Rubio-Godoy V, Bioley G, Guillaume P, Batard P, Speiser D, Luescher I, Cerottini JC, Romero P, Zippelius A.Alpha 3 domain mutants of peptide/MHC class I multimers allow the selective isolation of high avidity tumor-reactive CD8 T cells.J Immuno
  12902485
• Rufer N, Zippelius A, Batard P, Pittet MJ, Kurth I, Corthesy P, Cerottini JC, Leyvraz S, Roosnek E, Nabholz M, Romero P.Ex vivo characterization of human CD8+ T subsets with distinct replicative history and partial effector functions.Blood 2003 Sep 1;102(
  12750165
• Dietrich PY, Le Gal FA, Dutoit V, Pittet MJ, Trautman L, Zippelius A, Cognet I, Widmer V, Walker PR, Michielin O, Guillaume P, Connerotte T, Jotereau F, Coulie PG, Romero P, Cerottini JC, Bonneville M, Valmori D.Prevalent role of TCR alpha-chain in the se
  12734356
• Ayyoub M, Zippelius A, Pittet MJ, Rimoldi D, Valmori D, Cerottini JC, Romero P, Lejeune F, Liénard D, Speiser DE.Activation of human melanoma reactive CD8+ T cells by vaccination with an immunogenic peptide analog derived from Melan-A/melanoma antigen rec
  12576434
• Schnyder B, Lahm H, Pittet M, Schnyder-Candrian S.Mono- or dual-phosphorylation of akt kinase is regulated by distinct receptors that involve the common insulin receptor substrate.J Recept Signal Transduct Res 2002 Feb-Nov;22(1-4):213-28.
  12503617
• Romero P, Pittet M, Dutoit V, Zippelius A, Liénard D, Lejeune F, Guillaume P, Rimoldi D, Valmori D, Speiser DE, Cerottini JC.Therapeutic cancer vaccines based on molecularly defined human tumor antigens.Vaccine 2002 Dec 19;20 Suppl 4:A2-7.
  12477422
• Romero P, Valmori D, Pittet MJ, Zippelius A, Rimoldi D, Lévy F, Dutoit V, Ayyoub M, Rubio-Godoy V, Michielin O, Guillaume P, Batard P, Luescher IF, Lejeune F, Liénard D, Rufer N, Dietrich PY, Speiser DE, Cerottini JC.Antigenicity and immunogenicity of Mel
  12445283
• Dutoit V, Rubio-Godoy V, Pittet MJ, Zippelius A, Dietrich PY, Legal FA, Guillaume P, Romero P, Cerottini JC, Houghten RA, Pinilla C, Valmori D.Degeneracy of antigen recognition as the molecular basis for the high frequency of naive A2/Melan-a peptide mult
  12119345
• Pittet MJ, Zippelius A, Valmori D, Speiser DE, Cerottini JC, Romero P.Melan-A/MART-1-specific CD8 T cells: from thymus to tumor.Trends Immunol 2002 Jul;23(7):325-8.
  12103339
• Valmori D, Dutoit V, Schnuriger V, Quiquerez AL, Pittet MJ, Guillaume P, Rubio-Godoy V, Walker PR, Rimoldi D, Liénard D, Cerottini JC, Romero P, Dietrich PY.Vaccination with a Melan-A peptide selects an oligoclonal T cell population with increased functio
  11937585
• Speiser DE, Liénard D, Pittet MJ, Batard P, Rimoldi D, Guillaume P, Cerottini JC, Romero P.In vivo activation of melanoma-specific CD8(+) T cells by endogenous tumor antigen and peptide vaccines. A comparison to virus-specific T cells.Eur J Immunol 2002 M
  11870617
• Kerre TC, De Smet G, De Smedt M, Zippelius A, Pittet MJ, Langerak AW, De Bosscher J, Offner F, Vandekerckhove B, Plum J.Adapted NOD/SCID model supports development of phenotypically and functionally mature T cells from human umbilical cord blood CD34(+) c
  11861276
• Zippelius A, Pittet MJ, Batard P, Rufer N, de Smedt M, Guillaume P, Ellefsen K, Valmori D, Liénard D, Plum J, MacDonald HR, Speiser DE, Cerottini JC, Romero P.Thymic selection generates a large T cell pool recognizing a self-peptide in humans.J Exp Med 20
  11854361
• Speiser DE, Colonna M, Ayyoub M, Cella M, Pittet MJ, Batard P, Valmori D, Guillaume P, Liénard D, Cerottini JC, Romero P.The activatory receptor 2B4 is expressed in vivo by human CD8+ effector alpha beta T cells.J Immunol 2001 Dec 1;167(11):6165-70.
  11714776
• Pittet MJ, Speiser DE, Valmori D, Rimoldi D, Liénard D, Lejeune F, Cerottini JC, Romero P.Ex vivo analysis of tumor antigen specific CD8+ T cell responses using MHC/peptide tetramers in cancer patients.Int Immunopharmacol 2001 Jul;1(7):1235-47.
  11460305
• Pittet MJ, Zippelius A, Speiser DE, Assenmacher M, Guillaume P, Valmori D, Liénard D, Lejeune F, Cerottini JC, Romero P.Ex vivo IFN-gamma secretion by circulating CD8 T lymphocytes: implications of a novel approach for T cell monitoring in infectious and
  11390521
• Pittet MJ, Speiser DE, Liénard D, Valmori D, Guillaume P, Dutoit V, Rimoldi D, Lejeune F, Cerottini JC, Romero P.Expansion and functional maturation of human tumor antigen-specific CD8+ T cells after vaccination with antigenic peptide.Clin Cancer Res 2001
  11300475
• Speiser DE, Migliaccio M, Pittet MJ, Valmori D, Liénard D, Lejeune F, Reichenbach P, Guillaume P, Lüscher I, Cerottini JC, Romero P.Human CD8(+) T cells expressing HLA-DR and CD28 show telomerase activity and are distinct from cytolytic effector T cells.E
  11180110
• Valmori D, Dutoit V, Liénard D, Rimoldi D, Pittet MJ, Champagne P, Ellefsen K, Sahin U, Speiser D, Lejeune F, Cerottini JC, Romero P.Naturally occurring human lymphocyte antigen-A2 restricted CD8+ T-cell response to the cancer testis antigen NY-ESO-1 in m
  10969798
• Romero P, Pittet MJ, Valmori D, Speiser DE, Cerundolo V, Liénard D, Lejeune F, Cerottini JC.Immune monitoring in cancer immunotherapy.Ernst Schering Res Found Workshop 2000(30):75-97.
  10943317
• Pittet MJ, Speiser DE, Valmori D, Cerottini JC, Romero P.Cutting edge: cytolytic effector function in human circulating CD8+ T cells closely correlates with CD56 surface expression.J Immunol 2000 Feb 1;164(3):1148-52.
  10640724
• Speiser DE, Pittet MJ, Valmori D, Dunbar R, Rimoldi D, Liénard D, MacDonald HR, Cerottini JC, Cerundolo V, Romero P.In vivo expression of natural killer cell inhibitory receptors by human melanoma-specific cytolytic T lymphocytes.J Exp Med 1999 Sep 20;190
  10499916
• Pittet MJ, Valmori D, Dunbar PR, Speiser DE, Liénard D, Lejeune F, Fleischhauer K, Cerundolo V, Cerottini JC, Romero P.High frequencies of naive Melan-A/MART-1-specific CD8(+) T cells in a large proportion of human histocompatibility leukocyte antigen (HL
  10477554
• Valmori D, Pittet MJ, Vonarbourg C, Rimoldi D, Liénard D, Speiser D, Dunbar R, Cerundolo V, Cerottini JC, Romero P.Analysis of the cytolytic T lymphocyte response of melanoma patients to the naturally HLA-A*0201-associated tyrosinase peptide 368-376.Cance
  10463606
• Speiser DE, Valmori D, Rimoldi D, Pittet MJ, Liénard D, Cerundolo V, MacDonald HR, Cerottini JC, Romero P.CD28-negative cytolytic effector T cells frequently express NK receptors and are present at variable proportions in circulating lymphocytes from heal
  10382762
• Valmori D, Pittet MJ, Rimoldi D, Liénard D, Dunbar R, Cerundolo V, Lejeune F, Cerottini JC, Romero P.An antigen-targeted approach to adoptive transfer therapy of cancer.Cancer Res 1999 May 1;59(9):2167-73.
  10232604
• Romero P, Dunbar PR, Valmori D, Pittet M, Ogg GS, Rimoldi D, Chen JL, Liénard D, Cerottini JC, Cerundolo V.Ex vivo staining of metastatic lymph nodes by class I major histocompatibility complex tetramers reveals high numbers of antigen-experienced tumor-s
  9802976