Deciphering the anti-tumor T response in leukemia’s patients treated by immunotherapy
Responsable de l’encadrement : Yannick SIMONI
Tél : 06 99 30 66 62
Institut Cochin – Paris
Résumé du Projet de Stage
Multiple myeloma (MM) is a blood cancer (leukemia) of plasma B cells. Often, no symptoms are noticed initially. As it progresses, bone pain, anemia, kidney dysfunction, and infections may occur and lead to death. Multiple myeloma is considered treatable, but generally incurable. Recently, the development of engineered bi-specific antibodies opened a new era in immunotherapy. In the context of MM, bi-specific antibody treatment brings together T cells (CD3 antigen) and tumor cells (BCMA antigen), leading to tumor cells lysis by T cells. However, resistance appears to invariably occur, and some patients fail to respond to bi-specific antibody therapy. Recently, T cells receptor (TCR) analysis in MM patients treated with BCMAxCD3 bi-specific antibodies reveals a clonal expansion of T cells, suggesting an anti-tumoral T cells response induce by this treatment. Therefore, identification and characterization of tumor antigens specific T cells, represent an important axis of research in MM to improve patients’ response (e.g. Immune check point inhibitor antibodies, vaccination with tumor antigens…) in combination with the current treatment.
This M2 project aims to decipher in detail the anti-tumor T response in MM patients, before and after CD3xBCMA bi-specific treatment, in blood and bone marrow, by using cutting edge methods for data acquisition and analysis. Multiplex MHC class I tetramers assay coupled to mass-cytometry will allows us to screen up to 200 tumor antigens for each patient, and characterize phenotypically tumor-specific CD8 T cells for each identified epitope using high dimensional data analysis (see Publication list for details).
Dernières Publications en lien avec le projet :
- Simoni Y*, Becht E, Fehlings M, Loh CY, Koo SL, Teng KWW, Yeong JPS, Nahar R, Zhang T, Kared H, Duan K, Ang N, Poidinger M, Lee YY, Larbi A, Khng AJ, Tan E, Fu C, Mathew R, Teo M, Lim WT, Toh CK, Ong BH, Koh T, Hillmer AM, Takano A, Lim TKH, Tan EH, Zhai W, Tan DSW, Tan IB, Newell EW*. Bystander CD8(+) T cells are abundant and phenotypically distinct in human tumour infiltrates. Nature. 2018
- Simoni Y, Chng MHY, Li S, Fehlings M and Newell EW. Mass cytometry: a powerful tool for dissecting the immune landscape. Current Opinion in Immunology. 2018 (IF: 7.5)
- Simoni Y, Fehlings M and Newell EW. Multiplex MHC Class I Tetramer Combined with Intranuclear Staining by Mass Cytometry. Methods in Molecular Biology. 2019
- Simoni Y, Chapuis N. Diagnosis of Myelodysplastic Syndromes: From Immunological Observations to Clinical Applications. Diagnostics. 2022.
- Li S, Zhuang S, Heit A, Koo SL, Chow I, Kwok WW, Tan IB, Tan SWD, Simoni Y*, Newell EW*. Bystander CD4+ T cells infiltrate human tumors and are phenotypically distinct. OncoImmunology. 2022
Equipe d’Accueil :
Intitulé de l’Unité : Institut Cochin U1016 – Team Normal and pathological hematopoiesis
Nom du Responsable de l’Unité : Pr Michaela Fontenay and Pr Didier Bouscary
Nom du Responsable de l’Équipe : Dr. Yannick Simoni
Adresse : Institut Cochin 22 Rue Méchain, 75014 Paris