The metabolism, CAncer and immune REsponses (mCARE) INSERM team, created in 2006, focuses on the molecular basis of energy metabolism in cancers (lymphomas and lung cancers).

Our research strategy is to determine whether modulation of cancer cell metabolism and metabolic enzymes can modulate tumor growth, response to chemotherapy and the anticancer immune response.

In cancer research, identifying specificities of tumor cells compared with "normal" proliferating cells is considered the holy grail for the development of targeted therapies. Although diverse in origin, most cancer cells share characteristics including the ability to escape cell death and the use of different sources of energy. In the current paradigm, aerobic glycolysis is considered the central metabolic characteristic of cancer cells (the Warburg effect). However, recent data indicate that significant changes in other metabolic pathways are also needed, including amino acid, lipid and mitochondrial (OxPhos) metabolism. In this more complex picture, this variety of metabolic source could be a strength (creating endless possibilities for adaptation and drug resistance) or a weakness that could be targeted to eliminate cancer cells.

Our laboratory studies the molecular basis of tumor metabolism in cancers: how it can be targeted and how it may influence the anticancer immune responseon a continuum from fundamental mechanisms to the clinic. We are developing unique preclinical models and in vivo methods to study the metabolic dependency of tumor cells in their correct pathological microenvironment.

Projects

People
JE. Ricci

JE. RicciResearch Director
Mail jean-ehrland.ricci@univ-cotedazur.fr

People
J. Chiche

J. ChicheResearcher
Mail Johanna.CHICHE@univ-cotedazur.fr

GAPDH is a clinical biomarker of DLBCL response to R-CHOP and to metabolic inhibitors

About 40% of diffuse large B cell lymphoma (DLBCL) patients are refractory to the combined immunochemotherapy (R-CHOP) standard treatment. DLBCL is metabolically heterogeneous. We have shown that low levels of GAPDH, which predict poor R-CHOP response, are associated with OxPhos metabolism, mTORC1 signaling, and glutaminolysis. Inhibitors of these pathways improved the response of DLBCL mice and patients with low levels of GAPDH. Chiche et al. Cell Metabolism 2019

People
P. Meola

P. MeolaResearch engineer
Mail Pauline.Meola@unice.fr

People
R. Paul-Bellon

R. Paul-BellonResearch engineer
Mail Rachel.PAUL@univ-cotedazur.fr

People
S. Marchetti

S. MarchettiResearcher
Mail Sandrine.MARCHETTI@univ-cotedazur.fr

People
JE. Ricci

JE. RicciResearch Director
Mail jean-ehrland.ricci@univ-cotedazur.fr

People
E. Verhoeyen

E. VerhoeyenResearch Director
Mail Els.VERHOEYEN@univ-cotedazur.fr

Overexpression of GAPDH in T-cell lineage in a mouse model recapitulates AITL disease

We generated transgenic mice overexpressing GAPDH in T cells. We obserevd that those mice develop lymphoma that recapitulates key features of human Angioimmunoblastic T-cell Lymphoma (AITL), including activation of the noncanonical NF-kB pathway. Blocking NF-kB activity with an NIK inhibitor reduces human and mouse AITL growth. Mondragon et al. Cancer Cell 2019

People
A. Krug

A. KrugPhD student
Mail adrien.krug@etu.univ-cotedazur.fr

People
R. Paul-Bellon

R. Paul-BellonResearch engineer
Mail Rachel.PAUL@univ-cotedazur.fr

People
JE. Ricci

JE. RicciResearch Director
Mail jean-ehrland.ricci@univ-cotedazur.fr

Low PROTEIN diet increases tumor-infiltrating lymphocytes

Dietary restriction (DR) slows down tumor growth by increasing tumor immunosurveillance. We showed that a moderate reduction in dietary protein intake, compared with a reduction in carbohydrates, without overall calorie changes, activates the IRE1a/RIG1pathway in tumor cells resulting in an anticancer immune response in mice. Rubio-Patino et al. Cell Metabolism 2018

People
H. Issaoui

H. IssaouiPost-doctoral fellow
Mail hussein_issaoui1992@hotmail.fr

People
R. Paul-Bellon

R. Paul-BellonResearch engineer
Mail Rachel.PAUL@univ-cotedazur.fr

People
J. Chiche

J. ChicheResearcher
Mail Johanna.CHICHE@univ-cotedazur.fr

People
S. Marchetti

S. MarchettiResearcher
Mail Sandrine.MARCHETTI@univ-cotedazur.fr

People
JE. Ricci

JE. RicciResearch Director
Mail jean-ehrland.ricci@univ-cotedazur.fr

People
S. Marchetti

S. MarchettiResearcher
Mail Sandrine.MARCHETTI@univ-cotedazur.fr

Control of mitophagy by ARIH1 protects cancer cells from chemotherapy-induced death

Clearance of damaged mitochondria (mitophagy) is involved in the resistance to chemotherapy-induced death, but the main known regulators of mitophagy are not expressed in cancer cells. We showed that the RBR E3 ligase ARIH1 is expressed in several cancer cell types. ARIH1 controls PINK1-dependent mitophagy and sensitivity to chemotherapies. Villa et al. Cell Reports 2017

 

 

C3M
Mitochondrial network of HeLa cells

People
S. Nunez-Vasquez

S. Nunez-VasquezPost-doctoral fellow
Mail nunezvazquez.sonia@gmail.com

People
R. Paul-Bellon

R. Paul-BellonResearch engineer
Mail Rachel.PAUL@univ-cotedazur.fr

People
J. Chiche

J. ChicheResearcher
Mail Johanna.CHICHE@univ-cotedazur.fr

Publications

Focus

GAPDH Expression Predicts the Response to R-CHOP, the Tumor Metabolic Status, and the Response of DLBCL Patients to Metabolic Inhibitors.

Authors Chiche J, Reverso-Meinietti J, Mouchotte A, Rubio-Patiño C, Mhaidly R, Villa E, Bossowski JP, Proics E, Grima-Reyes M, Paquet A, Fragaki K, Marchetti S, Briere J, Ambrosetti D, Michiels JF, Molina TJ, Copie-Bergman C, Lehmann-Che J, Peyrottes I, Peyrade F, de Kerviler E, Taillan B, Garnier G, Verhoeyen E, Paquis-Flucklinger V, Shintu L, Delwail V, Delpech-Debiais C, Delarue R, Bosly A, Petrella T, Brisou G, Nadel B, Barbry P, Mounier N, Thieblemont C, Ricci JE

Cell metabolism Jun 2019

Other recent publications

Investigation of Possible Factors Influencing the Neutralizing Anti-SARS-CoV-2 Antibody Titer after Six Months from the Second Vaccination Dose in a Sample of Italian Nursing Home Personnel.

Authors Modenese A, Paduano S, Bellucci R, Marchetti S, Bruno F, Grazioli P, Vivoli R, Gobba F, Bargellini A

Antibodies (Basel, Switzerland) Sep 2022

Impact of global warming on weight in patients with heart failure during the 2019 heatwave in France.

Authors Roubille F, Matzner-Lober E, Aguilhon S, Rene M, Lecourt L, Galinier M, Ricci JE, Molinari N

ESC heart failure Sep 2022

IRE1α overexpression in malignant cells limits tumor progression by inducing an anti-cancer immune response.

Authors Martinez-Turtos A, Paul R, Grima-Reyes M, Issaoui H, Krug A, Mhaidly R, Bossowski JP, Chiche J, Marchetti S, Verhoeyen E, Chevet E, Ricci JE

Oncoimmunology Sep 2022

Show all publications

Patents

Patent Number : Patent Number: International patent number : WO2015/132163 A METHOD FOR PREDICTING THE RESPONSIVENESS A PATIENT TO A TREATMENT WITH AN ANTI-CD20 ANTIBODY

Co-inventors J. Chiche, J. Ricci, catherine Thieblemont

Patent Number : Patent Number: International patent number : WO2017/055484 METHODS FOR DETERMINING THE METABOLIC STATUS OF LYMPHOMAS

Co-inventors J. Chiche, J. Ricci, Catherine Thieblemont

Patent Number : Patent Number: International patent number : EP17305294.5 A METHOD FOR PREDICTING THE RESPONSIVENESS OF A PATIENT TO A TREATMENT WITH mTOR INHBITORS

Co-inventors J. Chiche, J. Ricci, Catherine Thieblemont

Show all patents