Photo of Mikael J. Pittet,  PhD

Mikael J. Pittet, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 643-6285


mpittet@mgh.harvard.edu

Mikael J. Pittet, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Associate Professor, Radiology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

My laboratory's specific aims include 1) the development of a therapeutic immunology program that focuses on novel and emerging treatment options against cancer based on the immune system, and 2) a basic program that concentrates on the discovery of basic aspects of immune cell dynamics in disease that could establish new paradigms for future translational efforts. We also argue that a critical barrier to progress in the field has been our limited ability to assess immune functions and drug effects in relevant experimental models and directly in complex in vivo environments. To shift current experimental research approaches, we combine genetic mouse models in which tumors are driven by common genetic alterations and resist standard therapy together with (clinically applicable) molecular imaging readouts to assess treatment responses. These models and approaches, together with patient sample analyses, are used to interrogate tumor microenvironments in vivo and should give new opportunities for discovery of contributions of the immune response to cancer and novel targets for therapeutic intervention.

Publications

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  • Spiegel A, Brooks MW, Houshyar S, Reinhardt F, Ardolino M, Fessler E, Chen MB, Krall JA, DeCock J, Zervantonakis IK, Iannello A, Iwamoto Y, Cortez-Retamozo V, Kamm RD, Pittet MJ, Raulet DH, Weinberg RA. Neutrophils suppress intraluminal NK-mediated tumor cell clearance and enhance extravasation of disseminated carcinoma cells. 2016. PubMed
  • Pucci F, Garris C, Lai CP, Newton A, Pfirschke C, Engblom C, Alvarez D, Sprachman M, Evavold C, Magnuson A, von Andrian UH, Glatz K, Breakefield XO, Mempel TR, Weissleder R, Pittet MJ. SCS macrophages suppress melanoma by restricting tumor-derived vesicle-B cell interactions. Science 2016. PubMed
  • Pfirschke C, Engblom C, Rickelt S, Cortez-Retamozo V, Garris C, Pucci F, Yamazaki T, Poirier-Colame V, Newton A, Redouane Y, Lin YJ, Wojtkiewicz G, Iwamoto Y, Mino-Kenudson M, Huynh TG, Hynes RO, Freeman GJ, Kroemer G, Zitvogel L, Weissleder R, Pittet MJ. Immunogenic Chemotherapy Sensitizes Tumors to Checkpoint Blockade Therapy. Immunity 2016; 44:343-54. PubMed
  • Ramasamy S, Saez B, Mukhopadhyay S, Ding D, Ahmed AM, Chen X, Pucci F, Yamin R, Wang J, Pittet MJ, Kelleher CM, Scadden DT, Sweetser DA. Tle1 tumor suppressor negatively regulates inflammation in vivo and modulates NF-κB inflammatory pathway. Proc Natl Acad Sci U S A 2016; 113:1871-6. PubMed
  • Miller MA, Gadde S, Pfirschke C, Engblom C, Sprachman MM, Kohler RH, Yang KS, Laughney AM, Wojtkiewicz G, Kamaly N, Bhonagiri S, Pittet MJ, Farokhzad OC, Weissleder R. Predicting therapeutic nanomedicine efficacy using a companion magnetic resonance imaging nanoparticle. Sci Transl Med 2015; 7:314ra183. PubMed
  • Garris CS, Pittet MJ. ER Stress in Dendritic Cells Promotes Cancer. Cell 2015; 161:1492-3. PubMed
  • Pfirschke C, Garris C, Pittet MJ. Common TLR5 mutations control cancer progression. Cancer Cell 2015; 27:1-3. PubMed
  • Miller MA, Zheng YR, Gadde S, Pfirschke C, Zope H, Engblom C, Kohler RH, Iwamoto Y, Yang KS, Askevold B, Kolishetti N, Pittet M, Lippard SJ, Farokhzad OC, Weissleder R. Tumour-associated macrophages act as a slow-release reservoir of nano-therapeutic Pt(IV) pro-drug. Nat Commun 2015; 6:8692. PubMed
  • Sistigu A, Yamazaki T, Vacchelli E, Chaba K, Enot DP, Adam J, Vitale I, Goubar A, Baracco EE, Remédios C, Fend L, Hannani D, Aymeric L, Ma Y, Niso-Santano M, Kepp O, Schultze JL, Tüting T, Belardelli F, Bracci L, La Sorsa V, Ziccheddu G, Sestili P, Urbani F, Delorenzi M, Lacroix-Triki M, Quidville V, Conforti R, Spano JP, Pusztai L, Poirier-Colame V, Delaloge S, Penault-Llorca F, Ladoire S, Arnould L, Cyrta J, Dessoliers MC, Eggermont A, Bianchi ME, Pittet M, Engblom C, Pfirschke C, Préville X, Uzè G, Schreiber RD, Chow MT, Smyth MJ, Proietti E, André F, Kroemer G, Zitvogel L. Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nat Med 2014; 20:1301-9. PubMed
  • Pittet MJ, Nahrendorf M, Swirski FK. The journey from stem cell to macrophage. Ann N Y Acad Sci 2014. PubMed
  • Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillère R, Hannani D, Enot DP, Pfirschke C, Engblom C, Pittet MJ, Schlitzer A, Ginhoux F, Apetoh L, Chachaty E, Woerther PL, Eberl G, Bérard M, Ecobichon C, Clermont D, Bizet C, Gaboriau-Routhiau V, Cerf-Bensussan N, Opolon P, Yessaad N, Vivier E, Ryffel B, Elson CO, Doré J, Kroemer G, Lepage P, Boneca IG, Ghiringhelli F, Zitvogel L. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science 2013; 342:971-6. PubMed
  • Garris C, Pittet MJ. Therapeutically reeducating macrophages to treat GBM. Nat Med 2013; 19:1207-8. PubMed
  • Squadrito ML, Etzrodt M, De Palma M, Pittet MJ. MicroRNA-mediated control of macrophages and its implications for cancer. Trends Immunol 2013. PubMed
  • Pucci F, Pittet MJ. Molecular pathways: tumor-derived microvesicles and their interactions with immune cells in vivo. Clin Cancer Res 2013. PubMed
  • Cortez-Retamozo V, Etzrodt M, Newton A, Ryan R, Pucci F, Sio SW, Kuswanto W, Rauch PJ, Chudnovskiy A, Iwamoto Y, Kohler R, Marinelli B, Gorbatov R, Wojtkiewicz G, Panizzi P, Mino-Kenudson M, Forghani R, Figueiredo JL, Chen JW, Xavier R, Swirski FK, Nahrendorf M, Weissleder R, Pittet MJ. Angiotensin II drives the production of tumor-promoting macrophages. Immunity 2013; 38:296-308. PubMed
  • Dutta P, Courties G, Wei Y, Leuschner F, Gorbatov R, Robbins CS, Iwamoto Y, Thompson B, Carlson AL, Heidt T, Majmudar MD, Lasitschka F, Etzrodt M, Waterman P, Waring MT, Chicoine AT, van der Laan AM, Niessen HW, Piek JJ, Rubin BB, Butany J, Stone JR, Katus HA, Murphy SA, Morrow DA, Sabatine MS, Vinegoni C, Moskowitz MA, Pittet MJ, Libby P, Lin CP, Swirski FK, Weissleder R, Nahrendorf M. Myocardial infarction accelerates atherosclerosis. Nature 2012; 487:325-9. PubMed
  • Etzrodt M, Cortez-Retamozo V, Newton A, Zhao J, Ng A, Wildgruber M, Romero P, Wurdinger T, Xavier R, Geissmann F, Meylan E, Nahrendorf M, Swirski FK, Baltimore D, Weissleder R, Pittet MJ. Regulation of monocyte functional heterogeneity by miR-146a and Relb. Cell Rep 2012; 1:317-24. PubMed
  • Cortez-Retamozo V, Etzrodt M, Newton A, Rauch PJ, Chudnovskiy A, Berger C, Ryan RJ, Iwamoto Y, Marinelli B, Gorbatov R, Forghani R, Novobrantseva TI, Koteliansky V, Figueiredo JL, Chen JW, Anderson DG, Nahrendorf M, Swirski FK, Weissleder R, Pittet MJ. Origins of tumor-associated macrophages and neutrophils. Proc Natl Acad Sci U S A 2012; 109:2491-6. PubMed
  • Rauch PJ, Chudnovskiy A, Robbins CS, Weber GF, Etzrodt M, Hilgendorf I, Tiglao E, Figueiredo JL, Iwamoto Y, Theurl I, Gorbatov R, Waring MT, Chicoine AT, Mouded M, Pittet MJ, Nahrendorf M, Weissleder R, Swirski FK. Innate response activator B cells protect against microbial sepsis. Science 2012; 335:597-601. PubMed
  • Leuschner F, Rauch PJ, Ueno T, Gorbatov R, Marinelli B, Lee WW, Dutta P, Wei Y, Robbins C, Iwamoto Y, Sena B, Chudnovskiy A, Panizzi P, Keliher E, Higgins JM, Libby P, Moskowitz MA, Pittet MJ, Swirski FK, Weissleder R, Nahrendorf M. Rapid monocyte kinetics in acute myocardial infarction are sustained by extramedullary monocytopoiesis. J Exp Med 2012; 209:123-37. PubMed
  • Lau KS, Cortez-Retamozo V, Philips SR, Pittet MJ, Lauffenburger DA, Haigis KM. Multi-scale in vivo systems analysis reveals the influence of immune cells on TNF-α-induced apoptosis in the intestinal epithelium. PLoS Biol. 2012; 10:e1001393. PubMed
  • Keliher EJ, Yoo J, Nahrendorf M, Lewis JS, Marinelli B, Newton A, Pittet MJ, Weissleder R. 89Zr-labeled dextran nanoparticles allow in vivo macrophage imaging. Bioconjug Chem 2011; 22:2383-9. PubMed
  • Pittet MJ, Weissleder R. Intravital imaging. Cell 2011; 147:983-91. PubMed
  • Leuschner F, Dutta P, Gorbatov R, Novobrantseva TI, Donahoe JS, Courties G, Lee KM, Kim JI, Markmann JF, Marinelli B, Panizzi P, Lee WW, Iwamoto Y, Milstein S, Epstein-Barash H, Cantley W, Wong J, Cortez-Retamozo V, Newton A, Love K, Libby P, Pittet MJ, Swirski FK, Koteliansky V, Langer R, Weissleder R, Anderson DG, Nahrendorf M. Therapeutic siRNA silencing in inflammatory monocytes in mice. Nat Biotechnol 2011. PubMed
  • Pittet MJ, Swirski FK. Monocytes link atherosclerosis and cancer. Eur J Immunol 2011; 41:2519-22. PubMed
  • Panizzi P, Nahrendorf M, Figueiredo JL, Panizzi J, Marinelli B, Iwamoto Y, Keliher E, Maddur AA, Waterman P, Kroh HK, Leuschner F, Aikawa E, Swirski FK, Pittet MJ, Hackeng TM, Fuentes-Prior P, Schneewind O, Bock PE, Weissleder R. In vivo detection of Staphylococcus aureus endocarditis by targeting pathogen-specific prothrombin activation. Nat Med 2011; 17:1142-6. PubMed
  • Da Silva N, Cortez-Retamozo V, Reinecker HC, Wildgruber M, Hill E, Brown D, Swirski FK, Pittet MJ, Breton S. A dense network of dendritic cells populates the murine epididymis. Reproduction 2011; 141:653-63. PubMed
  • Swirski FK, Wildgruber M, Ueno T, Figueiredo JL, Panizzi P, Iwamoto Y, Zhang E, Stone JR, Rodriguez E, Chen JW, Pittet MJ, Weissleder R, Nahrendorf M. Myeloperoxidase-rich Ly-6C+ myeloid cells infiltrate allografts and contribute to an imaging signature of organ rejection in mice. J Clin Invest 2010; 120:2627-34. PubMed
  • Nahrendorf M, Keliher E, Marinelli B, Waterman P, Feruglio PF, Fexon L, Pivovarov M, Swirski FK, Pittet MJ, Vinegoni C, Weissleder R. Hybrid PET-optical imaging using targeted probes. Proc Natl Acad Sci U S A 2010; 107:7910-5. PubMed
  • Swirski FK,Weissleder R,Pittet MJ. Heterogeneous In Vivo Behavior of Monocyte Subsets in Atherosclerosis. Arterioscler Thromb Vasc Biol 2009; 29:1424-32. PubMed
  • 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 to inflammatory sites. Science 2009; 325:612-6. PubMed
  • 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 nanoparticle. Neoplasia 2009; 11:459-68, 2 p following 468. PubMed
  • Pittet MJ. Behavior of immune players in the tumor microenvironment. Curr Opin Oncol 2009; 21:53-9. PubMed
  • 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 airway inflammation. J Clin Invest 2008; 118:4058-66. PubMed
  • 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; 105:7387-92. PubMed
  • Weissleder R, Pittet MJ. Imaging in the era of molecular oncology. Nature 2008; 452:580-9. PubMed
  • Pittet MJ, Mempel TR. Regulation of T-cell migration and effector functions: insights from in vivo imaging studies. Immunol Rev 2008; 221:107-29. PubMed
  • 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; 204:3037-47. PubMed
  • 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; 104:12457-61. PubMed
  • 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; 117:195-205. PubMed
  • 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; 103:10340-5. PubMed
  • 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; 25:129-41. PubMed
  • 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; 176:2330-6. PubMed
  • Pittet MJ, Swirski FK, Reynolds F, Josephson L, Weissleder R. Labeling of immune cells for in vivo imaging using magnetofluorescent nanoparticles. Nat Protoc 2007; 1:73-9. PubMed
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