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ILC2 functional manipulation at the single cell level for innovative cancer immunotherapy (Professor)

Applicant Jandus Camilla
Number 179727
Funding scheme PRIMA
Research institution Département de Pathologie et Immunologie Faculté de Médecine / CMU Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Immunology, Immunopathology
Start/End 01.02.2019 - 31.12.2024
Approved amount 1'362'472.00
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All Disciplines (2)

Discipline
Immunology, Immunopathology
Experimental Cancer Research

Keywords (6)

human; cancer; single cells; Innate lymphoid cells; reprogramming; epigenetic

Lay Summary (French)

Lead
Manipulation fonctionnelle des ILC2 au niveau de la cellule unique pour optimiser l'immunothérapie anticancéreuse
Lay summary
L'immunologie tumorale et l'immunothérapie ont récemment pris le devant de la scène dans la recherche sur le cancer. Il s'agit de traitements qui mobilisent les cellules immunitaires de l'organisme pour traquer les cellules cancéreuses dans l'organisme et les tuer. Les immunothérapies sont déjà utilisées dans les cliniques de tous les jours, mais seule une proportion limitée de patients répondent au traitement. Dans ce projet, nous prévoyons d'explorer comment les cellules lymphoïdes innées (ILC) affectent les réponses anti-tumorales.
Les ILC sont une famille de lymphocytes innés récemment découverts, divisés en 3 sous-populations fonctionnellement distincts. Les ILC se caractérisent par leur activation précoce et leur capacité à sécréter rapidement un grand nombre de messagers chimiques qui, à leur tour, alerteront l'ensemble de la machine immunitaire et imprimeront une polarité pro- ou anti-inflammatoire à la réponse immunitaire globale. Dans le domaine du cancer, le rôle des ILC reste mal compris. Nous avons déjà signalé que la sous-populations de ILC2 joue un rôle central dans l'établissement d'un nouvel axe immunosuppresseur dans différents types de tumeurs humaines. Ici, nous visons à comprendre quels sont les acteurs moléculaires impliqués dans cet axe. À cette fin, nous combinons l'analyse génétique et épigénétique au niveau des cellules individuelles d'échantillons de sang et de tissus de patients atteints de cancer, avec des essais fonctionnels in vitro et des évaluations in vivo dans des modèles murins de cancer. L'étude des mécanismes immunorégulateurs médiés par les ILC peut fournir de nouvelles cibles pour affiner et augmenter les taux de réponse globale aux thérapies immunitaires, et obtenir des réponses immunitaires bien orchestrées pour contrôler et éliminer les tumeurs.
Direct link to Lay Summary Last update: 04.09.2018

Responsible applicant and co-applicants

Employees

Publications

Publication
Immune Checkpoint and Telomerase Crosstalk Is Mediated by miRNA-138 in Bladder Cancer
El Ahanidi Hajar, El Azzouzi Meryem, Hafidi Alaoui Chaimae, Tetou Mohammed, Bensaid Mounia, Chaoui Imane, Benbacer Laila, Hassan Ilias, Oukabli Mohamed, Michaud Katarzyna, Ameur Ahmed, Al Bouzidi Abderrahmane, El Mzibri Mohammed, Jandus Camilla, Attaleb Mohammed (2022), Immune Checkpoint and Telomerase Crosstalk Is Mediated by miRNA-138 in Bladder Cancer, in Frontiers in Oncology, 11, 795242.
Static Adhesion Assay for Human Peripheral Blood Mononuclear Cells
Vanoni Giulia, Jandus Camilla, Trabanelli Sara (2022), Static Adhesion Assay for Human Peripheral Blood Mononuclear Cells, in BIO-PROTOCOL, 12(1), e4276.
PPARɣ drives IL-33-dependent ILC2 pro-tumoral functions
Ercolano Giuseppe, Gomez-Cadena Alejandra, Dumauthioz Nina, Vanoni Giulia, Kreutzfeldt Mario, Wyss Tania, Michalik Liliane, Loyon Romain, Ianaro Angela, Ho Ping-Chih, Borg Christophe, Kopf Manfred, Merkler Doron, Krebs Philippe, Romero Pedro, Trabanelli Sara, Jandus Camilla (2021), PPARɣ drives IL-33-dependent ILC2 pro-tumoral functions, in Nature Communications, 12(1), 2538-2538.
Healthy and Patient Type 2 Innate Lymphoid Cells are Differently Affected by in vitro Culture Conditions
Falquet Maryline, Ercolano Giuseppe, Jandus Peter, Jandus Camilla, Trabanelli Sara (2021), Healthy and Patient Type 2 Innate Lymphoid Cells are Differently Affected by in vitro Culture Conditions, in Journal of Asthma and Allergy, Volume 14, 773-783.
Tumor-specific cytolytic CD4 T cells mediate immunity against human cancer
Cachot Amélie, Bilous Mariia, Liu Yen-Cheng, Li Xiaokang, Saillard Margaux, Cenerenti Mara, Rockinger Georg Alexander, Wyss Tania, Guillaume Philippe, Schmidt Julien, Genolet Raphaël, Ercolano Giuseppe, Protti Maria Pia, Reith Walter, Ioannidou Kalliopi, de Leval Laurence, Trapani Joseph A., Coukos George, Harari Alexandre, Speiser Daniel E., Mathis Alexander, Gfeller David, Altug Hatice, Romero Pedro, et al. (2021), Tumor-specific cytolytic CD4 T cells mediate immunity against human cancer, in Science Advances, 7(9), 3348.
Severe COVID-19 patients exhibit an ILC2 NKG2D+ population in their impaired ILC compartment
Gomez-Cadena Alejandra, Spehner Laurie, Kroemer Marie, Khelil Myriam Ben, Bouiller Kevin, Verdeil Grégory, Trabanelli Sara, Borg Christophe, Loyon Romain, Jandus Camilla (2021), Severe COVID-19 patients exhibit an ILC2 NKG2D+ population in their impaired ILC compartment, in Cellular & Molecular Immunology, 18(2), 484-486.
Human primed ILCPs support endothelial activation through NF-κB signaling
Vanoni Giulia, Ercolano Giuseppe, Candiani Simona, Rutigliani Mariangela, Lanata Mariangela, Derré Laurent, Marcenaro Emanuela, Schneider Pascal, Romero Pedro, Jandus Camilla, Trabanelli Sara (2021), Human primed ILCPs support endothelial activation through NF-κB signaling, in eLife, 10, e58838.
Impact of Immunotherapy on CD4 T Cell Phenotypes and Function in Cancer
Saillard Margaux, Cenerenti Mara, Romero Pedro, Jandus Camilla (2021), Impact of Immunotherapy on CD4 T Cell Phenotypes and Function in Cancer, in Vaccines, 454.
Distinct and shared gene expression for human innate versus adaptive helper lymphoid cells
Ercolano Giuseppe, Wyss Tania, Salomé Bérengère, Romero Pedro, Trabanelli Sara, Jandus Camilla (2020), Distinct and shared gene expression for human innate versus adaptive helper lymphoid cells, in Journal of Leukocyte Biology, 108(2), 723-737.
Immunosuppressive Mediators Impair Proinflammatory Innate Lymphoid Cell Function in Human Malignant Melanoma
Ercolano Giuseppe, Garcia-Garijo Andrea, Salomé Bérengère, Gomez-Cadena Alejandra, Vanoni Giulia, Mastelic-Gavillet Beatris, Ianaro Angela, Speiser Daniel E., Romero Pedro, Trabanelli Sara, Jandus Camilla (2020), Immunosuppressive Mediators Impair Proinflammatory Innate Lymphoid Cell Function in Human Malignant Melanoma, in Cancer Immunology Research, 8(4), 556-564.
Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes
Pesce Silvia, Trabanelli Sara, Vito Clara Di, Greppi Marco, Obino Valentina, Guolo Fabio, Minetto Paola, Bozzo Matteo, Calvi Michela, Zaghi Elisa, Candiani Simona, Lemoli Roberto Massimo, Jandus Camilla, Mavilio Domenico, Marcenaro Emanuela (2020), Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes, in Cancers, E3504.
Optimized combinatorial pMHC class II multimer labeling for precision immune monitoring of tumor-specific CD4 T cells in patients
Rockinger Georg Alexander, Guillaume Philippe, Cachot Amélie, Saillard Margaux, Speiser Daniel E, Coukos Georges, Harari Alexandre, Romero Pedro J, Schmidt Julien, Jandus Camilla (2019), Optimized combinatorial pMHC class II multimer labeling for precision immune monitoring of tumor-specific CD4 T cells in patients, in Journal for ImmunoTherapy of Cancer, 8(1), e000435-e000435.
ILC2s: New Actors in Tumor Immunity
Ercolano Giuseppe, Falquet Maryline, Vanoni Giulia, Trabanelli Sara, Jandus Camilla (2019), ILC2s: New Actors in Tumor Immunity, in Frontiers in Immunology, 10, 2801.
CD56 as a marker of an ILC1-like population with NK cell properties that is functionally impaired in AML
Salomé Bérengère, Gomez-Cadena Alejandra, Loyon Romain, Suffiotti Madeleine, Salvestrini Valentina, Wyss Tania, Vanoni Giulia, Ruan Dan Fu, Rossi Marianna, Tozzo Alessandra, Tentorio Paolo, Bruni Elena, Riether Carsten, Jacobsen Eva-Maria, Jandus Peter, Conrad Curdin, Hoenig Manfred, Schulz Ansgar, Michaud Katarzyna, Della Porta Matteo Giovanni, Salvatore Silvia, Ho Ping-Chih, Gfeller David, Ochsenbein Adrian, et al. (2019), CD56 as a marker of an ILC1-like population with NK cell properties that is functionally impaired in AML, in Blood Advances, 3(22), 3674-3687.
Peripheral Innate Lymphoid Cells Are Increased in First Line Metastatic Colorectal Carcinoma Patients: A Negative Correlation With Th1 Immune Responses
Loyon Romain, Jary Marine, Salomé Bérengère, Gomez-Cadena Alejandra, Galaine Jeanne, Kroemer Marie, Romero Pedro, Trabanelli Sara, Adotévi Olivier, Borg Christophe, Jandus Camilla (2019), Peripheral Innate Lymphoid Cells Are Increased in First Line Metastatic Colorectal Carcinoma Patients: A Negative Correlation With Th1 Immune Responses, in Frontiers in Immunology, 10, 2121.

Collaboration

Group / person Country
Types of collaboration
Prof Mohamed Attaleb, Rabat Morocco (Africa)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
Prof M Delorenzi, Dr F Schütz Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof D Gfeller Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Prof Daniel Benamran, University Hosptial of of Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Gene Expression Core Facility EPFL Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
PD Dr Petros Tsantoulis, Unversity Hospital of Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
iGE3 Annual Meeting Talk given at a conference Cytotoxic CD4 T cells: new weapons in cancer immunotherapy 11.11.2021 Geneva, Switzerland Jandus Camilla;
Forum PhD school of life sciences 2021 Talk given at a conference Killer CD4 T cells: who are they? 25.06.2021 Geneva, Switzerland Jandus Camilla;
40mo congresso nazionale della società italiana di farmacologia Talk given at a conference PPARg drives IL-33-dependent ILC2 pro-tumoral functions 10.03.2021 Rome, Italy Ercolano Guiseppe;
ESMO Immuno-Oncology 2020 Virtual Congress Talk given at a conference NK cells, innate lympoid cells and cancer immunotherapy 09.12.2020 Virtual, Switzerland Jandus Camilla;
SITC Annual Meeting Talk given at a conference Tumor-specific cytolytic CD4 T cells mediate protetctive immunity against human cancer 09.11.2020 Washington, United States of America Jandus Camilla;
WIRM XIV Talk given at a conference Different culture conditions affect human ILC2 proliferation and phenotype 04.10.2020 Davos, Switzerland Falquet Maryline;
ESMO Immuno-Oncology Congress 2019 Talk given at a conference NK cells and ILCs and their checkpoints 11.11.2019 Geneva, Switzerland Jandus Camilla;
SSAI Annual meeting Talk given at a conference Innate lymphocytes: new avenues in immunotherapy? 05.09.2019 Lugano, Switzerland Jandus Camilla;
5th intern conference of translational medicine on pathogenesis and therapy of immunemediated diseases Poster Immunosuppressive mediators impair pro-inflammatory ILC functions in human malignant melanoma 16.05.2019 Milan, Italy Ercolano Guiseppe;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
UNIL-APNS post doc retreat Talk 31.10.2020 Lausanne, Switzerland Jandus Camilla;


Awards

Title Year
SITC Team Science Award to the Ludwig Cancer Lausanne Branch 2020

Abstract

Cancer is a leading cause of death worldwide, accounting for more than 8 million deaths per year. Cancer immunotherapy represents today the most promising cancer treatment since the development of the first chemotherapies. Recent results suggest that interventions based on a detailed understanding of the tumor microenvironment will be key to optimize immunotherapies. In that context, cytokine secreting cells are central players.A recently described family of rare, but potent cytokine secreting cells, called Innate Lymphoid Cells (ILCs), is emerging as key regulator of immunity. However, thus far ILCs have been neglected in the cancer field. We have been pioneering in identifying novel, dominant ILC2-dependent circuits of immunosuppression in cancer.I am in the extraordinary translational setting to dissect unique transcriptional and epigenetic programs of ILC2 directly in cancer patients, down to the single cell level, using highly sensitive technologies. I envision to decode for the first time immunosuppressive ILC2-signatures established in the tumor microenvironment and to determine the main factors prevailing in the tumor, facilitating immune escape. I will decipher the contribution of each factor in imprinting marks for cell polarization in cancer. By therapeutically interfering with these circuits in preclinical mouse models I will explore the impact of my discoveries directly in vivo, in view of phase I clinical trials. The innovative strategy of functionally reprogramming these cells in the tumor may curb immunosuppression, prove synergistic with other therapies and lead to clinical applications, beyond cancer.
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