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

ORCID
CALIANDRO Raphaël

CALIANDRO Raphaël

PH Institut Mutualiste Montsouris

Casrouge Armanda

Casrouge Armanda

IR Inserm

Fastenackels Solène

Fastenackels Solène

IE Sorbonne Université

Fornier Marie

Fornier Marie

Doctorante

 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

ORCID
Marodon Gilles

Marodon Gilles

CRHC Inserm, project leader

ORCID
NATUREL Marie

NATUREL Marie

Doctorante

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

ORCID
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.

SAR442085, a novel anti-CD38 antibody with enhanced antitumor activity against multiple myeloma. Kassem S, Diallo BK, El-Murr N, Carrié N, Tang A, Fournier A, Bonnevaux H, Nicolazzi C, Cuisinier M, Arnould I, Sidhu SS, Corre J, Avet-Loiseau H, Teillaud JL, van de Velde H, Wiederschain D, Chiron M, Martinet L, Virone-Oddos A. Blood. 2022 Feb 24;139(8):1160-1176. doi: 10.1182/blood.2021012448. PMID: 35201323

2.

BMFPs, a versatile therapeutic tool for redirecting a preexisting Epstein-Barr virus antibody response toward defined target cells. Gamain B, Brousse C, Rainey NE, Diallo BK, Paquereau CE, Desrames A, Ceputyte J, Semblat JP, Bertrand O, Gangnard S, Teillaud JL, Chêne A. Sci Adv. 2022 Feb 11;8(6):eabl4363. doi: 10.1126/sciadv.abl4363. Epub 2022 Feb 11. PMID: 35148183 Free PMC article.

3.

Tumor-Associated Tertiary Lymphoid Structures: A Cancer Biomarker and a Target for Next-generation Immunotherapy. Dieu-Nosjean MC. Adv Exp Med Biol. 2021;1329:51-68. doi: 10.1007/978-3-030-73119-9_3. PMID: 34664233

4.

Tertiary Lymphoid Structure-B Cells Narrow Regulatory T Cells Impact in Lung Cancer Patients. Germain C, Devi-Marulkar P, Knockaert S, Biton J, Kaplon H, Letaïef L, Goc J, Seguin-Givelet A, Gossot D, Girard N, Validire P, Lefèvre M, Damotte D, Alifano M, Lemoine FM, Steele KE, Teillaud JL, Hammond SA, Dieu-Nosjean MC. Front Immunol. 2021 Mar 8;12:626776. doi: 10.3389/fimmu.2021.626776. eCollection 2021. PMID: 33763071 Free PMC article

5.

Blockade of HVEM for Prostate Cancer Immunotherapy in Humanized Mice. Aubert N, Brunel S, Olive D, Marodon GCancers (Basel). 2021 Jun 16;13(12):3009. doi: 10.3390/cancers13123009. Free PMC article.

6.

Tumor-Associated Tertiary Lymphoid Structures: From Basic and Clinical Knowledge to Therapeutic Manipulation. Domblides C, Rochefort J, Riffard C, Panouillot M, Lescaille G, Teillaud JL, Mateo V, Dieu-Nosjean MC. Front Immunol. 2021 Jun 30;12:698604. doi: 10.3389/fimmu.2021.698604. eCollection 2021. PMID: 34276690 Free PMC article.

7.

Effective control of Staphylococcus aureus lung infection despite tertiary lymphoid structure disorganisation. Regard L, Martin C, Teillaud JL, Lafoeste H, Vicaire H, Ladjemi MZ, Ollame-Omvane E, Sibéril S, Burgel PR. Eur Respir J. 2021 Apr 15;57(4):2000768. doi: 10.1183/13993003.00768-2020. Print 2021 Apr. PMID: 33093122

8.

Intratumoral plasma cells: More than a predictive marker of response to anti-PD-L1 treatment in lung cancer? Teillaud JL, Dieu-Nosjean MC. Cancer Cell. 2022 Mar 14;40(3):240-243. doi: 10.1016/j.ccell.2022.02.008. Epub 2022 Feb 24. PMID: 35216677

9.

Recovery of central memory and naive peripheral T cells in Follicular Lymphoma patients receiving rituximab-chemotherapy based regimen. Milcent B, Josseaume N, Petitprez F, Riller Q, Amorim S, Loiseau P, Toubert A, Brice P, Thieblemont C, Teillaud JL, Sibéril S. Sci Rep. 2019 Sep 17;9(1):13471. doi: 10.1038/s41598-019-50029-y. PMID: 31530876 Free PMC article.

10.

Presence of T cells directed against CD20-derived peptides in healthy individuals and lymphoma patients. Milcent B, Josseaume N, Riller Q, Giglioli I, Rabia E, Deligne C, Latouche JB, Hamieh M, Couture A, Toutirais O, Lone YC, Jeger-Madiot R, Graff-Dubois S, Amorim S, Loiseau P, Toubert A, Brice P, Thieblemont C, Teillaud JL, Sibéril S. Cancer Immunol Immunother. 2019 Oct;68(10):1561-1572. doi: 10.1007/s00262-019-02389-7. Epub 2019 Sep 7. PMID: 31494742 Free PMC article.

11.

A novel combination of chemotherapy and immunotherapy controls tumor growth in mice with a human immune system. Burlion A, Ramos RN, Kc P, Sendeyo K, Corneau A, Ménétrier-Caux C, Piaggio E, Olive D, Caux C, Marodon GOncoimmunology. 2019 Apr 12;8(7):1596005. . eCollection 2019. Free PMC article.