Team 12

MITIC, Manipulation of Lymphocytes for Immunotherapy

Team Leaders: Emmanuel Scotet and Christelle Harly



Team 12a graphical abstract

Mechanisms of Lymphocytes’ development and functions

C. Harly & E. Mortier

The general interest of our Team is to understand in detail the molecular mechanisms underlying lymphocytes’ development and their functions. We are currently developing two basic research axes that respectively focus on the transcriptional mechanisms underlying innate lymphoid cells (ILC) development and functional programming, and cytokines’ mechanisms of action, which built on well-established basic research axes. We further aim to apply our knowledge to propose therapeutic solutions that answer unmet medical needs (eg. solid tumors). In line with this, we are developing a third axis that capitalizes on the collective expertise of the team members and the knowledge generated by the two basic axes to propose innovative strategies to manipulate lymphocytes for immunotherapy. Notably, we have recognized expertise in several rare and understudied populations of lymphocytes, (innate-like γδ and αβ T cells, and ILCs).
 

Team Members

Researchers and Faculty members

C. Harly                          CRCN    CNRS

E. Mortier                        DR2      CNRS

E. Scotet                        DR2      Inserm

X. Saulquin                     PR-EX   Nantes U

F. Konczak Del Gatto         MCF-HC Nantes U 

Technicians and Engineers

A. Quéméner                   IR-HC    Inserm 

M. Maillasson                  IR         Inserm 

D. Coulais                      IE         Inserm 

A. Trochel                       AI CDD  Inserm 

C. Costa-Martins              AI CDD  Inserm 

PhD Students

P. Machy                        4th yr      Nantes U

F. Boyer                         3rd yr      Nantes U

N. Belletoise                    2nd yr     Nantes U

C. Moyer                        1st yr      Nantes U

E. Artano                        1st yr      Nantes U 
 

Selected publications: 

 
  • Léger J., Artano E., Coulais D., Belletoise N., Fadhloun R., Kenney D., Bhandoola A., and Harly C. The transcription factor NFIL3 drives innate lymphoid cell specification from lymphoid progenitors. Immunity. 2025. S1074-7613(25)00435-2. doi: 10.1016/j.immuni.2025.10.005.
  • Joalland N., Quéméner A., Deshayes S., Humeau R., Maillasson M., LeBihan H., Salama A., Fresquet J., Remy S., Mortier E.*, Blanquart C.*, Guillonneau C.*, and Anegon I.* New soluble CSF-1R-dimeric mutein with enhanced trapping of both CSF-1 and IL-34 reduces suppressive tumor-associated macrophages in pleural mesothelioma. J. ImmunoTher. Cancer. 2025. 13(3):e010112. doi: 10.1136/jitc-2024-010112
  • Boutin L., Barjon C., Chauvet M., Lafrance L., Senechal E., Bourges D., Vigne E., and Scotet E. Camelid-derived Tcell engagers harnessing human γδ T cells as promising antitumor immunotherapeutic agents. Eur. J. Immunol. 2024. 54(8):e2350773. doi: 10.1002/eji.202350773
  • Nguyen N.K., Devilder M.C., Gautreau-Rolland L., Fourgeux C., Sinha D., Poschmann J., Hourmant M., Bressollette-Bodin C., Saulquin X., McIlroy D. A cluster of broadly neutralizing IgG against BK polyomavirus in a repertoire dominated by IgM. Life Sci. Alliance. 2023. 6(4):e202201567. doi: 10.26508/lsa.202201567



Team 12b graphical abstract

REPAIr: Research on lymphocyte Engineering and Profiling for Acute leukemia Immunotherapy

C. Retière & B. Clémenceau

 

The REPAIr team focuses on the immunobiology of NK and T lymphocytes in hematological malignancies, with a particular emphasis on the profiling and engineering of these cells for acute leukemia immunotherapy. Its activities are supported by a strong basic research and prospective clinical analyses conducted in close collaboration with hematology transplant clinicians in both pediatric and adult settings. These programs aim to improve our understanding of KIR/HLA interactions shaping NK cell repertoire, as well as T cell profiling accordingly to the nature of CAR receptors. The goal of our research is to identify, select and isolate human lymphoid cell subsets displaying specific phenotypes and/or functions that enhance their potential as optimal anti-tumor effectors for immunotherapeutic applications, and to select T lymphocytes capable of driving and controlling GVH-GVL reactions. We have developed several approaches aimed at engineering selected human lymphoid effectors to enhance anti-tumor functions directed against specific molecular targets. Recent programs dedicated to the grafting of Siglec ligands onto NK and T lymphocytes using click chemistry are expected to open up new avenues for improving lymphocyte tissue homing and anti-tumor functions. This program focused on selected and isolated human lymphoid effectors and their enhanced capacity to mediate potent anti-tumor activity both in vitro and in vivo. Collaborative programs have enabled profiling of specific lymphoid effector subsets (eg., NK and T cells) in leukemic patients and during immune reconstitution in the blood of hematopoietic stem cell transplant recipients, in a close collaboration with pediatric and adult hematopoietic stem cell transplantation clinicians. The REPAIr team is distinguished by its translational research spanning basic immunology to clinical applications, including completed and ongoing clinicals trials. 

 

Team Members

 

Researchers, Faculty members and Physicians

C. Retière              DR               EFS

K. Gagne               DR               EFS

E. Ferron               CR                EFS

L. Gautreau            MCF             Nantes U

B. Clémenceau       IR                 CHU

A. Grain                 MCUPH        CHU

P. Chevalier           PUPH           CHU

M. Julien               PH               CHU

Technicians and Engineers

J. Ollier                  Engineer      CHU

N. Legrand             Tech CDI       EFS

G. David                Tech CDI       EFS

E. Guiet                    Tech CN CDD

PhD Students

T. Clément            Nantes U

A. Joré                   Nantes U

 

Selected publications: 

 
  • Ferron E, Jullien M, Braud M, David G, Fourgeux C, Bastien M, Salameh P, Willem C, Legrand N, Walencik A, Guillaume T, Peterlin P, Garnier A, Lebourgeois A, Gagne K, Poschmann J, Chevallier P, Retière C. Molecular Interactions Between NK Cells and Acute Leukemic Cells: KIR2DL5 Drastically Limits NK Cell Responses. J. Clin. Immunol. 2025. 45(1):118. doi: 10.1007/s10875-025-01913-y.
  • Grain A, Ollier J, Le Calvez B, Guiet E, Thomas C, Couec ML, Camuset M, Rialland F, Eveillard M, Scotet E, Clémenceau B. Evaluation of multi-antigen targeting ADCC strategies in pediatric BCP-ALL. J. Immunother. Cancer. 2025. 13(12):e012552. doi: 10.1136/jitc-2025-012552.
  • Jullien M, Guillaume T, Le Bourgeois A, Peterlin P, Garnier A, Eveillard M, Le Bris Y, Bouzy S, Tessoulin B, Gastinne T, Dubruille V, Touzeau C, Mahé B, Blin N, Lok A, Vantyghem S, Sortais C, Antier C, Moreau P, Scotet E, Béné MC, Chevallier P. Phase I study of zoledronic acid combined with escalated doses of interleukine-2 for early in vivo generation of Vγ9Vδ2 T-cells after haploidentical stem cell transplant with posttransplant cyclophosphamide. 2024. American Journal of Hematology. 99:350-359 doi: 10.1002/ajh.27191

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Updated on 26 May 2026.