Accueil > TERI Department > Unconventional Tumor Epitopes, Antigen Presentation and T-cell Engineering
Unconventional Tumor Epitopes, Antigen Presentation and T-cell Engineering
Research summary
Mutation-associated neoepitopes play a major role in the response to immune checkpoint inhibitors and are currently used in cancer vaccine and T cell-based strategies. However, the development of these personalized approaches remains complex and poorly adapted to large numbers of tumors with a low mutational burden (TMB). There is therefore a major need to identify new families of tumor-specific antigens shared across patients to propose “off-the shelf” immunotherapies, especially in tumors characterized by a low TMB. Furthermore, amplification of the cellular immunity and epitope spreading are essential elements for the success of a vaccine strategy. It is now established in different anti-tumor vaccine approaches that the therapeutic response in patients is linked to the activation of cytotoxic T cells (CTL) recognizing not only the vaccine antigens, but also multiple others endogenous tumor antigens. The epitope spreading is the consequence of capture and presentation by tumor infiltrating dendritic cells (DCs) of tumor antigens released from tumor cells that were killed by anti-vaccine antigen CTL. In this context, DCs are highly specialized in the uptake, processing, and presentation of antigens, and many studies have identified the cDC1 subset as specialized in tumor antigen cross-presentation.
The team is thus focused on the identification and validation of shared neoepitopes derived from Human Endogenous Retroviruses (HERVs) and from alternative translational control of oncogenes. Several translational programs are developed as well as innovative approaches to improve the therapeutic efficacy of cancer vaccines by increasing cross-presentation by DCs and epitope spreading. Finally, we are also working on optimizing T cell receptor engineering to enhance the parameters associated with T cell activation against tumor cells expressing low-density targeted epitopes.
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Stephane DEPIL, MD, PhD
Stephane.depil@lyon.unicancer.frJenny VALLADEAU-GUILEMOND, DR2 INSERM
Jenny.valladeau-guilemond@lyon.unicancer.fr
Tel : 04 78 78 20 80
Team members
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TAMBURINI Jérôme
PUPH - Equipe S Depil / J Valladeau-Guilemond
Main fundings
Ligue contre le cancer
INCA
ARC
Agence Biomedecine
CLARA
ANR
France Relance
Region Rhône Alpes
ITMO Cancer
Fondation BMS
Publications
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Development of NK cell-based cancer immunotherapies through receptor engineering
Audrey Page, Nicolas Chuvin, Jenny Valladeau-Guilemond and Stéphane Depil Cellular & Molecular Immunology
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Guidelines for visualization and analysis of DC in tissues using multiparameter fluorescence microscopy imaging methods
Bayerl F, Bejarano DA, Bertacchi G, Doffin AC, Gobbini E, Hubert M, Li L, Meiser P, Pedde AM, Posch W, Rupp L, Schlitzer A, Schmitz M, Schraml BU, Uderhardt S, Valladeau-Guilemond J, Wilflingseder D, Zaderer V, Böttcher JP Eur J Immunol
Tumor Associated Dendritic cells in HumanSakref C., Bendriss-Vermare N., and Valladeau-Guilemond J Review in Methods in Molecular Biology. Springer Nature Ed.
Isolation and identification of dendritic cell subsets from human and mouse tumorsRocca Y*, Voissière A*, Valladeau-Guilemond J, Bendriss-Vermare N Methods Mol Biol.
TCR-engineered T cell therapy in solid tumors: State of the art and perspectivesE. Baulu, C. Gardet, N. Chuvin, S. Depil Sci Adv.
Netrin-1 blockade inhibits tumor associated Myeloid-derived suppressor cells, cancer stemness and alleviates resistance to chemotherapy and immune checkpoint inhibitorDucarouge B, Redavid AR, Victoor C, Chira R, Fonseca A, Hervieu M, Bergé R, Lengrand J, Vieugué P, Neves D, Goddard I, Richaud M, Laval PA, Rama N, Goldschneider D, Paradisi A, Gourdin N, Chabaud S, Treilleux I, Gadot N, Ray-Coquard I, Depil S, Decaudin D, Némati F, Marangoni E, Mery-Lamarche E, Génestie C, Tabone-Eglinger S, Devouassoux-Shisheboran M, Moore KJ, Gibert B, Mehlen P, Bernet A. Cell Death Differ
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Chimeric antigen receptor T-cells targeting IL-1RAP: a promising new cellular immunotherapy to treat acute myeloid leukemia
R Trad, W Warda, V Alcazer , M Neto da Rocha, A Berceanu, C Nicod, R Haderbache, X Roussel, Y Desbrosses, E Daguindau, F Renosi, C Roumier, L Bouquet, S Biichle, M Guiot, E Seffar, D Caillot, S Depil, E Robinet, Y Salma, E Deconinck, M Deschamps, C Ferrand J Immunother Cancer
Direct T-cell Presentation by cDC1: The Key Feature for Cancer Vaccine Success?Hubert M, Caux C, Valladeau-Guilemond J Cancer Immunol Res
Diversification of circulating and tumor-infiltrating plasmacytoid DCs towards the P3 (CD80+ PDL1-)-pDC subset negatively correlated with clinical outcomes in melanoma patientsSosa Cuevas E, Bendriss-Vermare N, Mouret S, De Fraipont F, Charles J, Valladeau-Guilemond J, Chaperot L, Aspord C Clin Transl Immunology
Identification of shared tumor epitopes from endogenous retroviruses inducing high avidity cytotoxic T cells for cancer immunotherapyP. Bonaventura, V. Alcazer, V. Mutez, L. Tonon, J. Martin, N. Chuvin, E. Michel, R. Boulos, Y. Estornes, J. Valladeau-Guilemond, A. Viari, C. Caux, S. Depil Sci Adv
Tumor burden and antigen-specific T cell magnitude represent major parameters for clinical response to cancer vaccine and TCR T cell therapyM. Mallet, R. E. Boulos, V. Alcazer, P. Bonaventura, Y. Estornes, N. Chuvin, S. Depil Eur J Cancer
HERVs characterize normal and leukemia stem cells and represent a source of epitopes for cancer immunotherapyV. Alcazer, P. Bonaventura, L. Tonon, E. Michel, V. Mutez, A. Viari, K. Metzeler, W. Hiddemann, A.Batcha, T. Herold, C. Caux, S. Depil Am J hematol
Radiotherapy as a means to increase the efficacy of T-cell therapy in solid tumorsP. A. Laurent, D. Morel, L. Meziani, S. Depil, E. Deutsch Oncoimmunology
Unique CLR expression patterns on circulating and tumor-infiltrating DC subsets correlated with clinical outcome in melanoma patientsSosa Cuevas E., Valladeau-Guilemond J., Mouret S., De Fraipont F., Charles J., Nathalie Bendriss-Vermare N., Chaperot L., Aspord C Front Immunol
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CD4+ T lymphocytes : major players in antitumor immune response
Leclair L and S. Depil Med Sci
T cell based immunotherapies in solid tumorsE. Baulu, A. Douge, N. Chuvin, J.-O. Bay, S. Depil. Bull Cancer
Type 1 conventional dendritic cells and interferons are required for spontaneous CD4+ and CD8+ T-cell protective responses to breast cancerMattiuz R, Brousse C, Ambrosini M, Cancel JC, Bessou G, Mussard J, Sanlaville A, Caux C, Bendriss-Vermare N, Valladeau-Guilemond J, Dalod M, Crozat K Clin Transl Immunology
Development of allogeneic CAR T-cellsV. Alcazer and S. Depil Bull Cancer
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BDCA1+ cDC2s, BDCA2+ pDCs and BDCA3+ cDC1s reveal distinct pathophysiologic features and impact on clinical outcomes in melanoma patients
Sosa Cuevas E, Ouaguia L, Mouret S, Charles J, De Fraipont F, Manches O, Valladeau-Guilemond J, Bendriss-Vermare N, Chaperot L, Aspord C Clin Transl Immunology
Hepatitis B virus exploits C-type lectin receptors to hijack cDC1s, cDC2s and pDCsOuaguia L, Dufeu-Duchesne T, Leroy V, Decaens T, Reiser JB, Sosa Cuevas E, Durantel D, Valladeau-Guilemond J, Bendriss-Vermare N, Chaperot L, Aspord C Clin Transl Immunology
Human Endogenous Retroviruses: Shaping the Innate Immune Response in CancersV. Alcazer, P. Bonaventura, S. Depil Cancers
Development of ‘off-the-shelf” allogeneic CAR T cells: state of the art, challenges and perspectivesS. Depil, P. Duchateau, S. Grupp, G. Mufti, L. Poirot Nat Rev Drug Discov
Towards “off the shelf” allogeneic CAR T cellB. Aftab, B. Sasu, J. Krishnamurthy, E. Gschweng, V. Alcazer, S. Depil Adv. Cell. Gene Ther
Expression of TAM-R in human immune cells and unique regulatory function of MERTK in IL-10 production by tolerogenic DCP. Giroud, S. Renaudineau, L. Gudefin, A. Calcei, T. Menguy, C. Rozan, J. Mizrahi, C. Caux, V. Duong and J. Valladeau-Guilemond Frontiers in Immunol.
IFN-III is selectively produced by cDC1 and predicts good clinical outcome in human breast cancerHubert M., Gobbini E., Couillault C., Vu Manh T.P., Kielbassa J., Rodriguez C, Doffin A., Treilleux I, Tredan O., Dalod M, BendrissVermare N., Caux C., Valladeau-Guilemond J Science Immunology