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.

Team

Mikael Pittet

PhD, Professor of Immunology, Faculty of Medicine, University of Geneva, Full Member, Ludwig Institute for Cancer Research, Geneva University Hospitals (HUG) & Swiss Cancer Center Leman (SCCL)

mikael.pittet@unige.ch PittetLab

Selected Publications

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

Imaging in the era of molecular oncology.

Weissleder R, Pittet MJ

Nature – 2008 Apr 3