Team 4

Innate Immunity and Cancer

Team leader : Yves Delneste

The team studies the innate immune system in physiological and pathological situations (cancer, chronic inflammatory diseases, acute and chronic infections).
Thanks to the clinicians integrated in the team, the projects are structured around a fundamental approach and a strong translational approach thanks to the collaborations set up with clinical services (CHU Angers, Institut de Cancérologie de l’Ouest Centre Paul Papin).

Historically, the team was interested in the biology of human macrophages and soluble receptors of innate immunity. More recently, in connection with the CRCI²NA thematic thread which aims at deciphering the tumor ecosystem, we have initiated projects addressing the links between tumor diversity and immune environment (dynamics of macrophage polarization).

Research axes

1. Biology of human macrophages

Macrophages are cells of myeloid origin present in all tissues of the body. True sentinels of the innate immune system, macrophages participate in many physiological mechanisms, such as antimicrobial defense, tissue repair and initiation/regulation of adaptive immune responses. A remarkable property of these cells is their functional plasticity, i.e. their ability to adapt their phenotype and functions to the nature of locally encountered signals.

Our work aims at :

– Identify the mechanisms of generation and characterize the functions of tumor-associated macrophages,
– Clarify the role of metabolists and immunometabolism in the functional polarization of macrophages

Our team has demonstrated the role of cytokines M-CSF and IL-34 and lactic acidosis in the generation of TAM-like macrophages in ovarian cancer.

Current projects aim to clarify (i) the diversity of TAMs in solid tumors (ovarian, lung) and hematological malignancies, (ii) the mechanisms of macrophage survival under stressful conditions and (iii) the epigenetic mechanisms involved in macrophage polarization.
 

2. Biology of soluble receptors of innate immunity

The soluble receptors of innate immunity (Pattern Recognition Molecules or PRM) were initially described as opsonins involved in the elimination of microbes and dead cells. Various studies have shown that they are also involved in the regulation of adaptive immune responses.
Although they are central actors of the innate immune system, the biology of MRPs remains poorly understood.

Our work aims to clarify the biology of :

– The clusterin molecule, initially described as an extracellular chaperone molecule and thought to be involved in the handling of extracellular hazard molecules,
– The cytokine IL-26 which behaves as a PRM modulating the inflammatory properties of nucleic acids.

Our team has demonstrated that IL-26 binds to nucleic acids and regulates their immunoregulatory properties.

3. Macrophages and myeloproliferative syndrome

Myeloproliferative neoplasms (MPN) are acquired clonal disorders characterized by an accumulation of mature blood cells. Their prognosis is linked to two major complications: short/medium term thrombosis and long term hematological changes. Among the hematological changes, progression to secondary acute myeloid leukemia is associated with a poor prognosis. The bone marrow microenvironment plays a key role in the pathogenicity of SMP by increasing molecular instability and promoting fibrosis and studies have shown that the myeloid compartment is altered (inflammatory phenotype).
Based on the cross expertise of TAM biology and molecular characterization of SMP, the objective of this emerging project is to identify TAM subtypes in SMP and to associate their phenotype with tumor cell diversity.

Yves Delneste, DR INSERM
Pascale Jeannin, PU-PH

Jean-François Augusto, PU-PH
Céline Beauvillain, MCU-PH
Odile Blanchet, MCU-PH
Anne Bouvier, PH
Louise-Marie Chevalier, PH
Marie-Christine Copin, PU
Laurane Cottin, PH
Dominique Couez, PU
Mathilde Hunault-Berger, PU-PH
Sandrine Lemoine, AHU
Damien Luque Paz, MCU-PH
Charline Miot, MCU-PH
Alain Morel, PU
Sandrine Nail-Billaud, MCU-PH
Corentin Orvain, PH
Isabelle Pellier, PU-PH
Caroline Poli, PH
Aline Schmidt-Tanguy, PU-PH
Jean-François Subra, PU-PH
Isabelle Tournier, CR
Valérie Ugo, PU-PH
Emeline Vinatier, PH

Simon Blanchard, ING
Nathalie Merillon, IE
Pascale Pignon, AI
Laurence Preisser, IE
Raffaella Soleti, IR
Luisa Vergori, IR

Benoît Brilland, PhD student
Maxime Corre, PhD student
Chloé Delépine, PhD student
Coralie Mallebranche, PhD student
Elena Menand, PhD student
Marine Monnier, PhD student
Sylvain Thépot, PhD student

Najia Jeroundi, Post-Doc
Léa Paolini, ATER

Alice Desouche, M2 student
Agathe Vely, M2 student

Organization of the team

The team is composed of scientists, biologists and clinicians from different fields of competence (immunology, hematology, nephrology) and expertise (cell biology, genomics/transcriptomics, …). The participation of biologists and clinicians in the team’s projects as well as the collaborations established with many clinical services of the CHU of Angers allows us to combine cognitive and translational research in each of our research projects.
The team has also established numerous collaborations with biology (Virology, Biochemistry) and clinical services of the CHU of Angers (Hepatology, MIR, gynecology) and of the Institut de Cancérologie de l’Ouest (Paul Papin site).
In order to structure our various local collaborations with clinical and biological services, the team has set up a 3I-Impact working group which aims at optimizing collaborations and integrating new skills to improve the quality of translational research in immunopathology.

The team is integrated in the LabEx IGO, the SIRIC ILIAD and the FHU GOAL.

The team is integrated in the Cancéropole Grand-Ouest and is a member of the Centre de Référence Déficits Immunitaires Héréditaires.

The translational research activities are carried out within the framework of the Structuring Project 3I-Impact supported by the University Hospital of Angers and the University of Angers; this project aims at reinforcing the emergence and the structuring of research projects between university teams and health care structures in the field of alterations of the immune system in severe pathologies (cancer, sepsis, chronic inflammatory diseases)

The team is integrated in the SFR ICAT and has access to all the technical and technological platforms.
The team also has a privileged access to the molecular biology platforms of the Hematology laboratory of the CHU of Angers (Pr. V Ugo) and of the functional genomics unit of the ICO (Pr A Morel and Dr I Tournier).

The team welcomes trainees (bachelor’s degree, master’s degree) from the science and health fields (Medicine and Pharmacy).

CRCI²NA - Institut de Recherche et d’Ingénierie de la Santé,
4 Rue Larrey,
49100 Angers

+33 (0)2 44 68 83 00

yves.delneste@univ-angers.fr

2022 :

Assessment of renal risk score and histopathological classification for prediction of end-stage kidney disease and factors associated with change in eGFR after ANCA-glomerulonephritis diagnosis.
Brilland B, Boud'hors C, Copin MC, Jourdain P, Henry N, Wacrenier S, Djema A, Samoreau C, Coindre JP, Cousin M, Riou J, Croue A, Saint-André JP, Subra JF, Piccoli GB, Augusto JF.  Frontiers in Immunology. 2022;13:834878.

IL-26 prevents HCV replication by interfering with viral RNA replication.
Beaumont E*, Larochette V*, Preisser L, Miot C, Pignon P, Blanchard S, Hansen BT, Dauve J, Poli C, Poranen MM, Lamourette P, Plaisance M, Morel A, Fickenscher H, Jeannin P*, Roingeard P*, Delneste Y*.
Journal of Hepatology. 2022;76(4):822-831

JAK2 V617F polycythemia vera and essential thrombocythemia: dynamic clinical features associated with long-term outcomes.
Sureau L, Buors C, Ianotto JC, Boyer F , Tanguy-Schmidt A, Roy L, Cayssials E, Chomel JC , Chauveau A, Orvain C, Mansier O, Ranta D, Robles M, Gyan E, Hérault O, Nimubona S, Marchand T, Lippert E, Riou J, Ugo V*, Luque Paz D*.
Blood Cancer Journal. 2021;11(7):135

2021:

Age‐related expression of IFN‐λ1 versus IFN-I and beta-defensins in the nasopharynx of SARS-CoV-2 infected individuals.
Gilbert C, Lefeuvre C, Preisser L, Pivert A, Soleti R, Blanchard S, Delneste Y, Ducancelle A, Couez D*, Jeannin P*.
Frontiers in Immunology. 2021;12:750279

Acetoacetate protects macrophages from lactic acidosis-induced mitochondrial dysfunction by metabolic reprograming.
Adam C*, Paolini L*, Gueguen N, Mabilleau G, Preisser L, Blanchard S, Pignon P, Manero F, Le Mao M, Morel A, Reynier P, Beauvillain C, Delneste Y*, Procaccio V*, Jeannin P*.
Nature Communications. 2021;12(1):7115

Functional pre-therapeutic evaluation by genome editing of variants of uncertain significance of essential tumor suppressor genes.
Billaud A, Chevalier LM, Augereau P, Frenel JS, Passot C, Campone M, Morel A.
Genome Medicine. 2021;13(1):174

Funding, Networks & Partners