Immune
microenvironment and
Immunotherapy

 

Marie-Caroline Dieu-Nosjean

Team Leader :

Dieu-Nosjean Marie-Caroline

Contact the team

The Team “Immune Microenvironment and Immunotherapy” includes scientists and clinicians with strong and complementary expertise in tumor immunology and immunotherapy in patients and mouse pre-clinical models. Team members are also involved in teaching and collaborate with hospitals and pharmaceutical companies at international level.

Based on our pioneering work describing the presence and the favorable prognostic value of Tertiary Lymphoid Structures (TLS) in cancer patients, with an in-depth analysis in lung cancer, our core focus is to advance research in the understanding of the cross-talk of TLS with the tumor microenvironment in lung and head/neck cancer patients and their manipulation in pre-clinical models.

Keywords : Tertiary lymphoid structure – Human and murine tumor immunology – T and B cell immunity – Therapeutic manipulation of TLS – Curative vaccination – Lung and head and neck carcinomas

Alveoli, bronchus and artery in murin lung Alveoli, bronchus and artery in murin lung
0Colocalization of blood vessels and sympathetic nerve fibers in the ear of mouse 0Colocalization of blood vessels and sympathetic nerve fibers in the ear of mouse
Germinal center with CD20+ B cells (green) and CD21+ follicular dendritic cells (orange) of a tertiary lymphoid structure associated with human lung tumor Germinal center with CD20+ B cells (green) and CD21+ follicular dendritic cells (orange) of a tertiary lymphoid structure associated with human lung tumor
T cell (green and orange) and B cell (blue) segregation within tertiary lymphoid structures in human lung tumor T cell (green and orange) and B cell (blue) segregation within tertiary lymphoid structures in human lung tumor
Development of tumor- associated tertiary lymphoid structures in lung tumor model Development of tumor- associated tertiary lymphoid structures in lung tumor model

The team members

Dieu-Nosjean Marie-Caroline

Dieu-Nosjean Marie-Caroline

DR2 Inserm, Team Leader

Bertolus Chloé

Bertolus Chloé

PU-PH AP-HP, Sorbonne Université, cheffe de service Chirurgie Maxillo-Faciale

Caliandro Raphaël

Caliandro Raphaël

PH Institut Mutualiste Montsouris

Fastenackels Solène

Fastenackels Solène

IE Sorbonne Université

 Gossot Dominique

Gossot Dominique

PH Institut Mutualiste Montsouris

Houel Ana

Houel Ana

Doctorante CIFRE, Sorbonne Université

 Lefèvre Marine

Lefèvre Marine

PH Institut Mutualiste Montsouris, cheffe de service d’Anatomo-pathologie

Lemoine François

Lemoine François

PU-PH Sorbonne Université

Lescaille Géraldine

Lescaille Géraldine

PU-PH AP-HP, Université de Paris, cheffe de service Odontologie

Mateo Véronique

Mateo Véronique

MCU Sorbonne Université

Panouillot Marylou

Panouillot Marylou

Doctorante CIFRE, Sorbonne Universite

Riffard Clémence

Riffard Clémence

Doctorante Sorbonne Université

Rochefort Juliette

Rochefort Juliette

MCU-PH AP-HP, Université de Paris

Seguin-Givelet Agathe

Seguin-Givelet Agathe

PU-PH, Institut Mutualiste Montsouris, Université Paris Nord, cheffe de service de Chirurgie Thoracique

Teillaud Jean-Luc

Teillaud Jean-Luc

DR Emérite Inserm

Viera Thibaut

Viera Thibaut

PH Institut Mutualiste Montsouris

Our research focus on 3 axes

1. Analysis of the immune functions of Tertiary Lymphoid Structures (TLS)

Our work has highlighted that the presence of TLS correlates with T-cell activation, Th1 phenotype, and cytotoxic orientation, and is required to license the prognostic value of tumor-infiltrating CD8+ T cells. Moreover, TLS-B cells correlate with the presence of plasma cells secreting antibodies against tumor antigens.

A specific focus is now to decipher the relationship between TLS, the molecular characteristics of tumor cells, and the functionality of B and T cell subsets in the tumor microenvironment in order to identify critical immune cell cross-talks involved in the development of efficient anti-tumor immunity.

2. Characterization of cells and molecules controlling TLS induction and maintenance

Our studies are aimed at exploring the cellular and molecular determinants that are critical in the induction and maintenance of TLS in the tumor microenvironment (lung and head and neck carcinomas).

By combining cellular and molecular approaches in mouse models and using human tumor biopsies, our goals are: i) to define the cell population(s) that are involved in the genesis of TLS under various inflammatory conditions; ii) to evaluate the role of neo-vasculature and nerve fibers in the making and maintenance of TLS; iii) to define soluble and membrane molecules that participate to TLS genesis.

3. Development of TLS-based immunotherapies

The presence of TLS in a large number of solid tumors has been associated with a more favorable prognostic.

Thus, the capacity of generating and maintaining functional TLS in the tumor microenvironment (TME) represents an attractive new immunotherapeutic approach to control tumor growth and possibly cure patients by inducing a potent long-lasting immune surveillance against cancer cells.

We are currently developing antibody (Ab)-based fusion molecules and other Ab formats to trigger/reinforce the presence of functional TLS in the TME. Their ability to recruit and stimulate tissue-lymphoid inducer like cells (LTi-like cells) in various models as well as different lipopolyplexe- and virus-based routes of in vivo administration are studied.

The opportunities

  • Identification and engineering of molecules that induce TLS neogenesis and stimulate their anti-tumoral role
  • Antibody-based combination therapy leading to reshaping the tumor microenvironment
  • Optimization of anti-cancer immunotherapy based on new therapeutic vaccines
  • Search of new prognostic and predictive biomarkers of cancers

Publications

1.

Kassem S., Diallo B.K., El-Murr N., Carrié N., Tang A., Fournier A., Bonnevaux H., Nicolazzi C., Cuisinier M., Arnould I., Sidhu S.S., Corre J., Avet-Loiseau H., Teillaud J.-L., van de Velde H., Wiederschain D., Chiron M., Martinet L., and Virone-Oddos, A. (2021) SAR442085, a novel anti-CD38 antibody with enhanced anti-tumor activity against Multiple Myeloma. Blood, in press.

2.

Gamain B., Brousse C., Rainey N., Diallo B.K., Paquereau C.-E., Desrames, A., Ceputyte J., Semblat J.-P., Bertrand O., Gangnard S., Teillaud, J.-L., and Chêne A. (2021) BMFPs, a versatile therapeutic tool for re-directing a pre-existing Epstein-Barr virus antibody response towards defined target cells. Sci Adv., in press.

3.

Dieu-Nosjean M-C. (2021) Chapter « Tumor-associated lymphoid structures: a cancer biomarker and a target for next-generation immunotherapy », Book « Tumor Microenvironment, Novel Concepts » edited by Dr. A. Birbrair. Springer Nature series entitled « Advances in Experimental Medicine and Biology ». Springer edition. eBook ISBN: 978-3-030-73119-9, Print ISBN: 978-3-030-73118-2. doi.org/10.1007/978-3-030-73119-9_3

4.

Germain G., Devi-Marulkar P., Knockaert S., Biton J., Kaplon H., Letaïef L., Goc J., Seguin-Givelet A., Gossot D., Girard N., Validire P., Lefevre M., Damotte D., Alifano M., Lemoine F., Steele K.E., Teillaud J.-L., Hammond S.A. and Dieu-Nosjean M.-C.  Tertiary lymphoid structure-B cells narrow regulatory T cells impact in lung cancer patients. Frontiers Immunol. 2021, March 08;12:article 626776. doi.org/10.3389/fimmu.2021.626776

5.

Domblides C, Rochefort J, Riffard C, Panouillot M, Lescaille G, Teillaud JL, Mateo V, Dieu-Nosjean MC. Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation. Front Immunol. 2021; 12:698604. doi: 10.3389/fimmu.2021.698604

6.

Regard L., Martin C., Teillaud J.-L., Lafoeste H., Vicaire H., Ladjemi M.Z., Ollame-Omvane E., Sibéril S., and Burgel P.-R. (2021) Effective control of Staphylococcus aureuslung infection despite tertiary lymphoid structure disorganisation. Eur Respir J., 15;57(4):2000768. doi: 10.1183/13993003.00768-2020.

7.

Casadesús A.V., Deligne C., Diallo B.K., Sosa K., Josseaume N., Mesa C., León K., Hernández T., Teillaud J.-L. (2020). A rationally-engineered IL-2 improves the antitumor effect of anti-CD20 therapy. Oncoimmunol 2020. 9(1):1770565. doi: 10.1080/2162402X.2020. 1770565.

8.

Milcent B., Josseaume N., Petitprez F, Riller Q., Amorim S., Loiseau P., Toubert A., Brice P., Thieblemont C., Teillaud J.-L., and Sibéril S. (2019) Recovery of central memory and naive peripheral T cells in Follicular Lymphoma patients receiving rituximab-chemotherapy based regimen. Sci. Rep. , 9(1):13471. doi: 10.1038/s41598-019-50029-y.

9.

Milcent B., Josseaume N., Riller Q., Giglioli I., Rabia E., Deligne C., Latouche J.-B., Hamieh M., Couture A., Toutirais O., Lone Y.C., Jeger-Madiot R., Graff-Dubois S., Amorim S., Loiseau P., Toubert A., Brice P., Thieblemont C., Teillaud J.-L., and Sibéril S. Presence of T cells directed against CD20-derived peptides in healthy individuals and lymphoma patients. Cancer Immunol Immunother 2019, 68(10) : 1561-1572. doi: 10.1007/s00262-019-02389

10.

Althammer S., Heng Tan T., Spitzmüller A., Rognoni L., Wiestler T., Herz T., Widmaier M., Rebelatto M., Kaplon K., Damotte D., Alifano M., Hammond S.A., Dieu-Nosjean M.-C., Ranade K., Schmidt G., Higgs B., Steele K. Automated image analysis of NSCLC biopsies to predict response to anti-PD-L1 therapy. J. ImmunoTher Cancer 2019, 7(1):121. doi: 10.1186/s40425-019-0589-x.