Team
Translational Immunology & Immunotherapy in Chronic Diseases

Dpt: Environnement, Reproduction, Infections, Cancer

Our research activities

Our unifying theme is to understand disease development, and to identify novel biomarkers or dysfunctional pathways based on the in depth analysis of the immune landscape in different chronic diseases, in order to develop new therapeutic approaches. We will focus on different chronic inflammatory diseases for which we previously developed a clinical and scientific expertise, and for which patient cohorts and biological samples (i.e., blood, plasma, and tissue biopsies) are already available with ethical agreements. These diseases and altered conditions are cancers (hepatocellular carcinoma and melanoma), chronic infections (hepatitis B virus [HBV]- and HBV/hepatitis D virus [HDV]), and transplantation (liver and kidney), all of which share the common feature of non-resolving inflammation. Such inflammatory condition is characterized by the persistence of an inflammatory leukocyte infiltrate, with increased levels of pro-inflammatory factors (i.e., cytokines and chemokines), and dysregulated metabolism. In all these diseases, dendritic cells (DC) ‒at least one of their subsets (e.g., cDC1 or PDC) ‒ are altered and could be manipulated to restore homeostasis. These innate cells have the advantage to initiate and regulate immune responses. Their targeting may, in theory, restore the entire immune response. In addition of sharing non-resolving inflammation, studying immune dysregulations in cancer (or chronic viral diseases) and graft rejection mechanisms in transplantation is complementary and can be considered as a mirror image. We are convinced that synergy can be achieved by the parallel analysis of immune escape (cancer or chronic infections) and over-stimulation (graft rejection), since detrimental phenomena described on one side could be exploited for beneficial effect on the other side. Our guiding principle is that identification of dysregulated immune cellular, metabolic, or signaling pathways paves the way for developing novel therapeutic approaches to restore functional immune responses through DC targeting. Our ultimate goal is to patent our data and to conduct interventional clinical studies based on ‒or guided by‒ the identified biomarkers or immune signatures, in order to improve patient care.

Philippe SAAS

Team leader

Thomas DECAENS

Team leader, PU-PH CHUGA

Medical team See the whole team

Our research axes

The objective of this work package is to study how features associated with chronic diseases and non-resolving inflammation may modulate dendritic cell crosstalk with the whole immune landscape, modifying frequencies or functions of immune cell subsets in the blood or tissues, in link with dysregulated immunometabolism or altered expression of molecular patterns (e.g., immune checkpoints, C-type lectin receptors, SIGLECs…).

This work program represents a transdisciplinary initiative to integrate social science perspectives into our existing research. It explores an emerging research field focused on the interplay between social determinants and health trajectories, particularly in chronic liver diseases such as hepatocellular carcinoma.

Our major publications

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HBV and HBsAg strongly reshape the phenotype, function, and metabolism of DCs according to patients' clinical stage

Dumolard L, Gerster T, Chuffart F, Decaens T, Hilleret MN, Larrat S, Saas P, Jouvin-Marche…

Hepatol Commun. 2025 Jan 29;9(2):e0625. doi: 10.1097/HC9.0000000000000625. PMID: 39878655; PMCID: PMC11781764.

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MCT1 lactate transporter blockade re-invigorates anti-tumor immunity through metabolic rewiring of dendritic cells in melanoma

Niveau C, Cettour-Cave M, Mouret S, Sosa Cuevas E, Pezet M, Roubinet B, Gil H,…

Nat Commun. 2025 Jan 27;16(1):1083. doi: 10.1038/s41467-025-56392-x. PMID: 39870647; PMCID: PMC11772620.

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Nanostructured lipid carriers based mRNA vaccine leads to a T cell-inflamed tumour microenvironment favourable for improving PD-1/PD-L1 blocking therapy and long-term immunity in a cold tumour model

Fournier C, Mercey-Ressejac M, Derangère V, Al Kadi A, Rageot D, Charrat C, Leroy A,…

EBioMedicine. 2025 Feb;112:105543. doi: 10.1016/j.ebiom.2024.105543. Epub 2025 Jan 9. PMID: 39793480; PMCID: PMC11774803.

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Liver cancer in ovo models for preclinical testing

Garcia P, Wang Y, Viallet J, Mehdi NEH, Montaut E, Decaens T, Emadali A, Macek…

FASEB J 2024 Sep 15;38(17):e70029. doi: 10.1096/fj.202401416R. PMID: 39215630.

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Maternal imprinting and determinants of neonates' immune function in the SEPAGES mother-child cohort

Manches O, Um K, Boudier A, Maddouri Y, Lyon-Caen S, Bayat S, Slama R, Philippat…

Front Immunol. 2023 Apr 4;14:1136749. doi: 10.3389/fimmu.2023.1136749. PMID: 37081891; PMCID: PMC10111372.

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An innovative plasmacytoid dendritic cell line-based cancer vaccine primes and expands antitumor T-cells in melanoma patients in a first-in-human trial

Charles J, Chaperot L, Hannani D, Bruder Costa J, Templier I, Trabelsi S, Gil H,…

Oncoimmunology 2020 Apr 12;9(1):1738812. doi: 10.1080/2162402X.2020.1738812. PMID: 32313721; PMCID: PMC7153838

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Immunologic Features of Patients With Advanced Hepatocellular Carcinoma Before and During Sorafenib or Anti-programmed Death-1/Programmed Death-L1 Treatment

Macek Jilkova Z, Aspord C, Kurma K, Granon A, Sengel C, Sturm N, Marche PN,…

Clin Transl Gastroenterol 2019 Jul;10(7):e00058. doi: 10.14309/ctg.0000000000000058. PMID: 31295151; PMCID: PMC6708670.

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Our collaborations

  • • Academic
  • ( Vall d’Hebron University Hospital, Barcelona, Spain; Icahn School of Medicine, Mount Sinai, New York, USA; German Cancer Research Center and University Hospital Tübingen, Germany; Ougadougou hospital, Burkina Faso; CRCL, Lyon,
  • Institute of Hepatology of Lyon; Platform for Translational Oncometabolomics, CNRS, INSERM, Univ. Montpellier).
  • • Private Companies
  • Inovotion [Grenoble], Transgene [Strasbourg/Lyon], Nestris Pharma [Lyon], Genosciences Pharma [Marseille], ICOA [Orléans], GlycoDiag [Orléans], CEA-Leti [Grenoble]

Our technologies

  • Multiparametric flow cytometry (supervised and unsupervised analysis)
  • Immuno-metabolism (flow cytometry-based method SCENITH)
  • Immune functional assays (proliferation, differentiation, cytotoxicity, cytokines…)
  • Preclinical experimental models
  • Bio-informatics