Cancer, Immune Control and Escape
Our goal is to study the immune microenvironment of human tumors and its interactions with tumor cells to find new prognosis markers and predictive markers of the therapeutic response, and to identify tumor drivers of the immune contexture. The effect of therapeutic interventions, with monoclonal antibodies in particular, is under investigation.
Our work focus on:
- The study of the immune contexture of lung carcinomas and renal cell primary and metastatic carcinomas. We study the cell densities and functionalities of B and T cells, plasma cells and the antibodies produced, dendritic cells (DCs), and NK cells, together with the role of tertiary lymphoid structures in the generation and maintenance of effector and memory antitumor immune responses.
- The study of tumor-derived drivers of the immune contexture in lung carcinoma, renal cell carcinoma and colorectal cancers. We are defining molecular and cellular mechanisms by which tumor cells shape their local immune contextures.
- The study of the effect of inflammation on tumor cells and on the immune microenvironment. This is investigated i) by studying the impact of COPD on the immune contexture in lung cancers; ii) analyzing the consequences of TLR7 expression and triggering on tumor cell survival, tumor progression and on resistance to chemotherapy.
- The study of the impact of antibody therapy on immune surveillance and adaptive anti-tumor response. The vaccine effect of antibody therapy is studied in patients with lymphoma treated with anti-CD20 antibody as well as in CD20 tumor murine models. Our goal is to characterize changes arising in T-cell compartments, to identify relevant T-cell epitopes and to optimize the vaccine effect by evaluating combination treatments (antibodies, cytokines).
Our approaches combine in situ analysis of the composition, density, and organization of innate and adaptive immune cells, combined with transcriptomics analyses on human tumors from large cohorts of patients made available through collaborations with medical departments. In silico bioinformatics approaches are used in parallel. Studies on the vaccine effects of therapeutic antibodies are performed on cells from peripheral blood of lymphoma patients. Various animal models are also used for mechanistic studies and validation of the concepts, both for lymphoma and lung cancers.
Team Leaders : Isabelle CREMER (Pr), Jean-Luc TEILLAUD (Dr)
Team members : Diane DAMOTTE (Pr), Marie-Caroline DIEU-NOSJEAN (Dr), Hervé FRIDMAN (Pr), Pierre-Emmanuel JOUBERT (Dr), Catherine SAUTES-FRIDMAN (Pr), Sophie SIBERIL (Dr), Pierre VALIDIRE (Pr).
Contact details : 01 44 27 91 00 Email: firstname.lastname@example.org
- Abes, R., Gélizé, E., Fridman, W.H., and Teillaud, J.-L. (2010) Long-lasting anti-tumor protection by anti-CD20 antibody through cellular immune response. Blood. 116: 926-34.
- Cherfils-Vicini, J., Platonova S., Laurans L., Validire P., Caliandro R., Magdelenat P., Mami-Chouaib F., Dieu-Nosjean M.C., Fridman W.H., Damotte D., Sautès-Fridman C., and Cremer I. (2010) Triggering of TLR7 and TLR8 expressed by human lung cancer induces cell survival and chemoresistance. J. Clin. Invest. 120: 1285-97.
- Platonova, S., Cherfils-Vicini, J., Damotte, D., Crozet, L., Vieillard, V., Validire, P., André, P., Dieu-Nosjean, M.-C., Alifano, M., Régnard, J.-F., Fridman, W.-H., Sautès-Fridman, C., and Cremer, I. (2011) Profound coordinated alterations of intratumoral NK cell phenotype and function in lung carcinoma. Cancer Res. 71: 5412-22.
- Fridman W.H., Pagès F., Sautès-Fridman C., and Galon J. (2012) The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 12: 298-306.
- Remark, R., Alifano, M., Cremer, I., Lupo, A., Dieu-Nosjean, M.-C., Riquet, M., Crozet, L., Ouakrim, H., Goc, J., Cazes, A., Fléjou, J.-F., Gibault, L., Verkarre, V., Régnard, J.-F., Pagès, O.N., Oudard, S., Mlecnik, B, Sautès-Fridman C, Fridman W.-H., and Damotte, D. (2013) Characteristics and clinical impacts of the immune environments in colorectal and renal cell carcinoma lung metastases: influence of tumor origin. Clin. Cancer Res. 19:4079-91.
- Goc, J., Germain, C., Vo-Bourgais, T.K., Lupo, A., Klein, C., Knockaert, S., de Chaisemartin, L., Ouakrim, H., Becht, E., Alifano, M., Validire, P., Remark, R., Hammond, S.A., Cremer, I., Damotte, D., Fridman, W.-H., Sautès-Fridman, C., and Dieu-Nosjean M.-C. (2014) Dendritic Cells in Tumor-Associated Tertiary Lymphoid Structures Signal a Th1 Cytotoxic Immune Contexture and License the Positive Prognostic Value of Infiltrating CD8 T Cells. Cancer Res. 74:705-15.
- Germain, C., Gnjatic, S., Tamzalit, F., Knockaert, S., Remark, R., Goc J., Lepelley, A., Becht, E., Katsahian, S., Bizouard, G., Validire, P., Damotte, D., Alifano, M., Magdelenat, P., Cremer, I., Teillaud, J.-L., Fridman, W.-H., Sautès-Fridman, C., and Dieu-Nosjean, M.-C. (2014) Presence of B Cells in Tertiary Lymphoid Structures is Associated with a Protective Immunity in Lung Cancer Patients. Am. J. Respir. Crit. Care Med. 189: 832-44.
- Giraldo, N.A., Becht, E., Remark, R., Damotte, D., Sautès-Fridman C., and Fridman, W.-H. (2014) The immune contexture of primary and metastatic human tumors. Curr. Opin. Immunol. 27:8-15.
Link to PubMed