Immunotherapies, in particular those targeting T lymphocytes (LT), have shown convincing results in many tumors but very little in breast cancer despite the presence of an important immune infiltrate. It is therefore necessary to develop new targets/strategies to direct the immune system towards an effective anti-tumor response in this pathology.
LT activation is mediated by antigen-presenting cells, in particular dendritic cells (DCs). Conventional type I dendritic cells (cDC1) seem to be very interesting. Indeed, our group and others have shown the functional superiority of cDC1 to present tumor Ag to CD8+ T cells. Moreover, we have shown for the first time the infiltration of primary breast tumors by cDC1 and observed that there are correlated with good patient prognosis in many types of cancer. In human breast tumor, cDC1 specifically produced a particular interferon (IFN) named type III interferon (IFN-III) which is able to potentialize an antitumor immune response and which is also correlated to a good patient prognosis.
However, the precise role of cDC1 and other DCs in the establishment of an anti-tumor immune response or in response to immunotherapies is not well known in humans. Thus, in order to answer the numerous questions that arise, my group is developing three complementary research axes on:
The role of DCs and IFN-III in the immune surveillance of the early phases of cancer;
The identification of IFN-III effects on the tumor microenvironment and in the blood;
The clinical impact of different DC populations on the response to immunotherapies and the role of each of those different DC populations in the tumor microenvironment.
Immunofluorescence microscopy of cDC1 in human tissues by coupling in situ hybridization with antibody staining. Doffin AC, Gobbini E, Hubert M and Valladeau-Guilemond J.European Journal Immunol. In press.
Tumor Associated Dendritic cells in Human. Sakref C., Bendriss-Vermare N., and Valladeau-Guilemond J. Review in Methods in Molecular Biology. Springer Nature Ed.In press
Isolation and identification of dendritic cell subsets from human and mouse tumors. Rocca Y*, Voissière A*, Valladeau-Guilemond J, Bendriss-Vermare N. Methods Mol Biol. In press.
Identification of shared tumor epitopes from endogenous retroviruses inducing high-avidity cytotoxic T cells for cancer immunotherapy. Bonaventura P, Alcazer V, Mutez V, Tonon L, Martin J, Chuvin N, Michel E, Boulos RE, Estornes Y, Valladeau-Guilemond J, Viari A, Wang Q, Caux C, Depil S. Science Advances. 2022 Jan 28;8(4).
Type 1 conventional dendritic cells and interferons are required for spontaneous CD4+ and CD8+ T-cell protective responses to breast cancer. Mattiuz 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. 2021 Jul 14;10(7).
IFN-III is selectively produced by cDC1 and predicts good clinical outcome n human breast cancer. Hubert 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. 5(46).
Expression of TAM-R in human immune cells and unique regulatory function of MERTK in IL-10 production by tolerogenic DC. P. Giroud, S. Renaudineau, L. Gudefin, A. Calcei, T. Menguy, C. Rozan, J. Mizrahi, C. Caux, V. Duong and J. Valladeau-Guilemond. Frontiers in Immunol. Vol 11. p2207. 2020
Cold Tumors: A Therapeutic Challenge for Immunotherapy; Bonaventura P, Shekarian T, Alcazer V, Valladeau-Guilemond J, Walsesia-Wittmann S, Amigorena S, Caux C and Depil S.. 2019. Immunol. Feb 8;10:168.
Human Tumor-Infiltrating Dendritic Cells: From in Situ Visualization to High-Dimensional Analyses. Hubert M, Gobbini E, Bendriss-Vermare N, Caux C, Valladeau-Guilemond J. Cancers. 2019. Jul 30;11(8). Review
Human natural killer cells promote cross-presentation of tumor cell-derived antigens by dendritic cells. Deauvieau, F., Ollion, V., Doffin, A. C., Achard, C., Fonteneau, J. F., Verronese, E., Durand, I., Ghittoni, R., Marvel, J., Dezutter-Dambuyant, C., Walzer, T., Vie, H., Perrot, I., Goutagny, N., Caux, C., & Valladeau-Guilemond, J.International journal of cancer, 136(5), 1085–1094.
Human XCR1+ dendritic cells derived in vitro from CD34+ progenitors closely resemble blood dendritic cells, including their adjuvant responsiveness, contrary to monocyte-derived dendritic cells. Balan, S., Ollion, V., Colletti, N., Chelbi, R., Montanana-Sanchis, F., Liu, H., Vu Manh, T. P., Sanchez, C., Savoret, J., Perrot, I., Doffin, A. C., Fossum, E., Bechlian, D., Chabannon, C., Bogen, B., Asselin-Paturel, C., Shaw, M., Soos, T., Caux, C., Valladeau-Guilemond, J., and Dalod, M. (Co-last author). 2014. J Immunol. 2014.193(4):1622-1635.
A novel regulation of PD-1 Ligands on Mesenchymal Stromal Cells through MMP-mediated proteolytic cleavage. Dezutter-Dambuyant C, Durand I, Alberti L, Bendriss-Vermare N, Valladeau-Guilemond J, Duc A, Magron A, Morel AP, Sisirak V, Rodriguez C, Cox D, Olive D, Caux C. 2015. OncoImmunology 5(3):e1091146
Immune cell dysfunctions in breast cancer patients detected through whole blood multi-parametric flow cytometry assay. Verronèse E, Delgado A, Valladeau-Guilemond J, Garin G, Guillemaut S, Tredan O, Ray-Coquard I, Bachelot T, N’Kodia A, Bardin C, Rigal C, Pérol D, Caux C*, Ménétrier-Caux C* ( *co-last authorship) 2015. OncoImmunology 5(3):e1100791
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