Team involved in this project :

• Ghiringhelli François (PU-PH) Contact : fghiringhelli@cgfl.fr
• Sylvain Ladoire, (PU-PH, HDR)
• Fanny Chalmin (PhD)
• Emeric Limagne (PhD)
• Cédric Rébé (PhD, HDR)
• Marion Thibaudin (PhD)
• Laura Kalfeist (PhD Student)
• Anaïs Perrichet (PhD Student)
• Susy Daumoine (TR)
• Léa Hampe (TR)
• Alis Ilié (TR)
• Lisa Nuttin (TR)

It has been recently shown that the immune system can make a decisive contribution to the therapeutic efficacy of conventional anticancer immune therapies (chemotherapy and radiotherapy). Our goal is to design chemo-immunotherapeutic protocols tailored to every patient.

We foster our interest on NSCLC, digestive cancer and breast cancer. Our strategy is to modelize human treatment with chemoimmunotherapy or targeted therapies plus immunotherapy in preclinical animal models. We design models of resistant to classical treatment to first explain the mechanisms of resistance and thus to develop innovative strategies to circumscribe immunoresistance.

We currently address the role of fibroblast and TGF beta in immunoresistance in breast cancer, the role of IL1 in the efficacy of chemoimmunotherapies in Lung and digestive cancers, the role of MAPK pathway in immunoresistance in lung cancer and finally we decipher the role of CD4 T cells in their capacity to tune efficacy of checkpoint inhibitors.

• Caroline Truntzer (PhD)
• Valentin Derangère (MCU PH)
• David Rageot (TR)

Image analysis:

We have skills to develop scripts mainly dedicated to brightfield image analysis such as standard staining (HE, trichrome) or immunohistochemistry staining (DAB or AEC chromogens) on large or small cohort. We are also able to edit AI models to classify tissue through a whole slide image using machine learning or deep learning strategy. Features extracted from image can also be linked to clinical data to evaluate patients’ prognosis for instance.

Next Generation Sequencing data analysis:

We provide skills for the analysis of sequencing data, including single-cell RNAseq, RNAseq and Whole Exome (WES) data. Raw data are processed through adapted bioinformatics pipelines and statistical analysis dedicated to high dimensional setting are then used to link these data with clinical variables of interest.

Team involved in this project :

• Mickaël Rialland (MCU, HDR)
• Jean-Louis Connat (Professeur émérite)
• Sabrina Perrey (Technicienne)
• Alois Dusuel (Ingénieur d’étude)
• Trinh-Le-Vi Kieu (Ingénieur d’étude Labex LipiSTIC)
• Emma Groetz (PhD)
• Léa Pierre (PhD)

Metabolism reprogramming is a hallmark of cancers and one aproach to kill cancer cells is to interfere with the metabolic rewiring. We are interested in understanding the role of fatty acid reprogramming in cancer cells and their heterotypic interactions with immune cells. Moreover, we evaluate the effect of dietary lipids on cancer progression and metabolism regulation.

Team involved in this project :

• • VEGRAN Frédérique (PhD, HDR, CR1)
  • BRUCHARD Mélanie (PhD)

• SADISSOU Ibrahim (PhD – Post-doc)
• HIBOS Christophe (PhD)
• GEINDREAU Mannon (PhD)

Lymphoid cell family is made up of innate and adaptive immune populations.
During the establishment of a tumor, the cells from the immune system lose their effectiveness. Understanding the mechanisms governing the differentiation, activation, migration and exhaustion of T lymphocytes, as well as the impact of treatments, is a required step to ultimately identify strategies for restoring the anti-tumor immune response. In this context, we direct our research towards the exploration of the non-canonical functions of NLRP3 in T lymphocytes and their impact on the tumor microenvironment and response to treatment.

ILCs are innate immune cells discovered in the late 2000s. Their role in the anti-tumor immune response remains to be deciphered. The second aim of our group is to understand their functions, not only in the tumor environment but also during the response to therapies. Our previous results show that ILC could act as a conductor in the establishment of a response to treatment. Thus, their study could allow the identification of new therapeutic strategies to improve the recruitment of immune cells as well as their activity.

Team involved in this project :

Permanent Researchers :

• • Aires Virginie (Associate Professor)
  • Delmas Dominique (Professor, Group leader)
  • Hermetet François (Associate Professor)
  • Dr Pierre-Benoit Pagès

Non-Permanent Researchers :

• • Sghaier Randa (Post-Doctoral student)
  • Belhadj Sahla(Post-Doctoral student)
  • Cornebise Clarisse (PhD, 2nd year)
  • Mathey Aline (PhD, 3rd year)
  • Perus Maude (PhD, 1st year)
  • Mammar Elodie (Master’s 2-degree student, AgroSup Engineering School, Dijon)
  • Miahle Aurélie (Master’s 2-degree student, Health Engineering-Pathway Design and Optimization of Health Products, Faculty of Pharmacy, Lyon)
  • Pires Vivien (Master’s 2-degree student, University of Burgundy)

Contact: dominique.delmas@u-bourgogne.fr

The “Bioactive Molecules and Health (BMH)” research group is conducting transdisciplinary translational research, to evaluate the impact of bioactive compounds, extracts or formulations on health and on degenerative diseases (cancers, inflammatory and immune disorders, age-related pathologies), with two major axes, one fundamental and translational, the other aimed at industrial valorization:

• Axis 1: Bioactive molecules & lipid metabolism-early markers and mechanisms of disease progression

This research axis, initiated in 2010, is intended to be translational and is based on multidisciplinary approaches, combining both preclinical animal models and clinical research on patients with progressive pathologies (i.e. cancers) or evolving toward therapeutic failure. This work is carried out in close collaboration with different teams of the UMR1231 research center (Epidemiology of Cancers, Biochemistry, Oncology and Physiopathology of Dyslipidemia), the Clinical Investigation Center, the Hepatogastroenterology and digestive cancer Department of the University Hospital of Dijon, the Anticancer Center Georges-François Leclerc (CGFL) of Dijon, as well as the “Eye and Nutrition” team of the INRAE institute of Dijon. In addition, this work is integrated to the 5th axis “Management of treatment failures” and to the structuring network “Ionizing Radiation in BIOlogie, combined therapies and Molecular Imaging-RIBIOTHIM-onco” of the Cancéropôle Grand-Est, as well as to the the LipSTIC Laboratory of Excellence, which was created in 2012 and renewed in 2017.

The main goals of this axis are:

• a) To identify early markers of cancer onset and progression
• b) To identify early and predictive markers of patient response to treatments in the energetic metabolism of tumors and especially in lipid metabolism
• c) To assess the role of the tumor microenvironment and tumor metabolism in cancer cells progression and response to therapeutic agents
• d) To evaluate the potential use of bioactive molecules such as polyphenols or fatty acids as preventive agents and/or therapeutic adjuvants when combined to various conventional chemotherapies, radiotherapy or immunotherapies.

• Axis 2: Bioactive molecules – Health- Industrial valorization

With a view to identifying new drugs, our research group is studying the preventive or potential therapeutic properties of bioactive molecules or formulations, in relation to diverse pathologies (degenerative diseases such as AMD, cancers, inflammation, autoimmune diseases…), with a special focus on their ability to delay the pathology onset or on their capacity to improve the sensitivity to conventional therapies. This latter is of clinical importance, since it may help in reducing treatments thresholds, toxicity and may contribute to enhance therapeutic success. This research axis, with a high valorization potential for companies, for the evaluation of xenobiotics, alicaments and natural molecules for nutritional or therapeutic purposes (Figure 2) aims to:

• 1)determine the « Health » effects of nutraceuticals, cosmeceuticals in various in vitro and in vivo models in order to provide health claims or to produce proof of concept for the use of these molecules;
• 2)optimizing formulations (combinations of several compounds and determining synergistic, additive or antagonistic effects) and determining the safety of formulations.
• 3) to provide scientific expertise to industrialists in the fields of immunology, inflammation and the health evaluation of their bioactive compounds.

d) Expertise and support in carrying out research projects are provided with the possibility of establishing research and development contracts under the research tax credit.

• • MIRJOLET Céline (PhD, HDR)

• LADJOHOUNLOU Riad (PhD – Post-doc)
• BOUSTANI Jihane (3ème année, PhD, MD)

Radiotherapy (RT) is one of the major players in the treatment of cancer, along with surgery, chemotherapy and now immunotherapy (IT). It has many indications, alone or in combination with other treatments.

Historically, RT is delivered to patients in fractions/sessions of 2-3 Gy (normofractionated regimen) making it possible to treat large volumes while limiting toxicities. Advances in radiotherapy techniques (image-guided IMRT, stereotaxy, etc.) make it possible to deliver high doses per fraction (hypofractionation of up to 20 Gy per fraction) by minimizing the organs at risk near the tumor and thus limiting radiation-induced toxicities.

Radiotherapy has a direct action on the survival of tumor cells but also on the immune system. Depending on the RT administration conditions (fractionation scheme, particles used, irradiated volumes, dose rate, etc.), the radiation-induced immune response may vary.

In our team, we are studying the impact of these RT parameters on the anti-tumor immunoactivating and pro-tumor immunosuppressive response in order to optimize combinations of RT with appropriate immunotherapies.

Figure 1 : Radiotherapy in dependence of the fractionation schedule recruits different type of immune cells and can modulate the immunotherapy target expression (Boustani et al., 2019, Cancers)