Pittet lab
Our goal is to acquire missing knowledge to find better ways to fight cancer. Our areas of expertise are immunology and immunotherapy. We are part of the Department of Pathology and Immunology at the University of Geneva, and are physically located in the AGORA Cancer Research Center in Lausanne. Our work has identified how certain cancers are regulated by various immune cells, including cytotoxic T cells, regulatory T cells, macrophages, monocytes, neutrophils and dendritic cells, all of which are considered drug targets in cancer immunotherapy. We are also using a variety of approaches, including intravital imaging, to better understand how drugs targeting components of the immune system work in vivo, and how these treatments could be improved rationally to be effective against a wider range of tumors and in more patients. ...
Research projects
Myeloid Cell Discovery
Myeloid cells belong to the innate immune system and include monocytes, macrophages, neutrophils and dendritic cells, among others. These cells can modulate key cancer-related activities and affect virtually all types of cancer treatment; however, we have a limited understanding of the complexity and functions of these cells and how they might best be exploited therapeutically to fight cancer. In this program, we are comprehensively mapping myeloid (and other) cells in tumors of patients and experimental models. Once the myeloid cell states are discovered, we exploit the information obtained to generate hypotheses about the functions of these states and to guide the design of functional studies to test these hypotheses. In doing so, we are able to distinguish between cells that do and do not promote tumor growth, and to discover molecular pathways and myeloid cell states that could be exploited for therapeutic purposes.
Real-Time PK/PD Imaging
What happens after an anticancer drug is administered? Where does it go? How does it work? Why does it sometimes fail to control cancer? In this program, we seek to answer these questions by combining two complementary tools: i) single-cell "omics", which provide high-dimensional information about the cells under study and how they are perturbed by drugs, and ii) intravital imaging, which we exploit to discover drug actions in real time and in the geographic context of the tissue being analyzed. This allows us to define where the drug accumulates (drug biodistribution), on which cells it binds (drug pharmacokinetics, PK), and how these cells and their neighbors respond to treatment (drug pharmacodynamics, PD). Through this approach, we can discover how the body and its constituent cells functionally respond to drugs, what mechanisms define treatment success or failure, and how to modify a treatment to make it more effective.
Latest publications
Convergent inducers and effectors of T cell paralysis in the tumour microenvironment.
Hanahan D, Michielin O, Pittet MJ
Nature reviews. Cancer – 2024 Oct 24
Circadian tumor infiltration and function of CD8(+) T cells dictate immunotherapy efficacy.
Wang C, Zeng Q, Gül ZM, (...), Simonetta F, Pittet MJ, Scheiermann C
Cell – 2024 May 2
Pharmacological Polarization of Tumor-Associated Macrophages Toward a CXCL9 Antitumor Phenotype.
Enbergs N, Halabi EA, Goubet AG, (...), Garris CS, Pittet MJ, Weissleder R
Advanced science – 2024 Feb 11
Dendritic cells as shepherds of T cell immunity in cancer.
Pittet MJ, Di Pilato M, Garris C, Mempel TR
Immunity – 2023 Sep 8
Dual TLR9 and PD-L1 targeting unleashes dendritic cells to induce durable antitumor immunity.
Fernandez-Rodriguez L, Cianciaruso C, Bill R, (...), Dixon KO, Pittet MJ, Zippelius A
Journal for immunotherapy of cancer – 2023 May
Team
Other members
Selected Publications
CXCL9:SPP1 macrophage polarity identifies a network of cellular programs that control human cancers.
Bill R, Wirapati P, Messemaker M, (...), Pai SI, Sade-Feldman M, Pittet MJ
Science (New York, N.Y.) – 2023 Aug 3
A neutrophil response linked to tumor control in immunotherapy.
Gungabeesoon J, Gort-Freitas NA, Kiss M, (...), Weissleder R, Klein AM, Pittet MJ
Cell – 2023 Mar 30
Dendritic cells direct circadian anti-tumour immune responses.
Wang C, Barnoud C, Cenerenti M, (...), Pittet MJ, Jandus C, Scheiermann C
Nature – 2022 Dec 5
Clinical relevance of tumour-associated macrophages.
Pittet MJ, Michielin O, Migliorini D
Nature reviews. Clinical oncology – 2022 Mar 30
CXCR6 positions cytotoxic T cells to receive critical survival signals in the tumor microenvironment.
Di Pilato M, Kfuri-Rubens R, Pruessmann JN, (...), Kobold S, Pittet MJ, Mempel TR
Cell – 2021 Aug 2
Resident Kupffer cells and neutrophils drive liver toxicity in cancer immunotherapy.
Siwicki M, Gort-Freitas NA, Messemaker M, (...), Weissleder R, Klein AM, Pittet MJ
Science immunology – 2021 Jul 2
Tumor-infiltrating dendritic cell states are conserved across solid human cancers.
Gerhard GM, Bill R, Messemaker M, Klein AM, Pittet MJ
The Journal of experimental medicine – 2021 Jan 4
Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations across Individuals and Species.
Zilionis R, Engblom C, Pfirschke C, (...), Levantini E, Pittet MJ, Klein AM
Immunity – 2019 Apr 9
Successful Anti-PD-1 Cancer Immunotherapy Requires T Cell-Dendritic Cell Crosstalk Involving the Cytokines IFN-γ and IL-12.
Garris CS, Arlauckas SP, Kohler RH, (...), Zippelius A, Weissleder R, Pittet MJ
Immunity – 2018 Dec 11
Recording the wild lives of immune cells.
Pittet MJ, Garris CS, Arlauckas SP, Weissleder R
Science immunology – 2018 Sep 7
Osteoblasts remotely supply lung tumors with cancer-promoting SiglecFhigh neutrophils.
Engblom C, Pfirschke C, Zilionis R, (...), Scadden DT, Weissleder R, Pittet MJ
Science (New York, N.Y.) – 2017 Dec 1
In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway in anti-PD-1 therapy.
Arlauckas SP, Garris CS, Kohler RH, (...), Anthony RM, Weissleder R, Pittet MJ
Science translational medicine – 2017 May 10
The role of myeloid cells in cancer therapies.
Engblom C, Pfirschke C, Pittet MJ
Nature reviews. Cancer – 2016 Jul
SCS macrophages suppress melanoma by restricting tumor-derived vesicle-B cell interactions.
Pucci F, Garris C, Lai CP, (...), Mempel TR, Weissleder R, Pittet MJ
Science (New York, N.Y.) – 2016 Mar 17
Immunogenic Chemotherapy Sensitizes Tumors to Checkpoint Blockade Therapy.
Pfirschke C, Engblom C, Rickelt S, (...), Zitvogel L, Weissleder R, Pittet MJ
Immunity – 2016 Feb 9
Origins of tumor-associated macrophages and neutrophils.
Cortez-Retamozo V, Etzrodt M, Newton A, (...), Swirski FK, Weissleder R, Pittet MJ
Proceedings of the National Academy of Sciences of the United States of America – 2012 Jan 30
Intravital imaging.
Pittet MJ, Weissleder R
Cell – 2011 Nov 23
Identification of splenic reservoir monocytes and their deployment to inflammatory sites.
Swirski FK, Nahrendorf M, Etzrodt M, (...), Libby P, Weissleder R, Pittet MJ
Science (New York, N.Y.) – 2009 Jul 31