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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:

  1. 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.
  2. 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.
  3. 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.
  4. 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 Leader : Isabelle CREMER (Pr).

Team members : Carine BROUSSE (Dr), Diane DAMOTTE (Pr), Marie-Caroline DIEU-NOSJEAN (Dr), Hervé FRIDMAN (Pr emeritus), Pierre-Emmanuel JOUBERT (Dr), Laila LETAIEF (Dr), Audrey LUPO (Dr), Catherine SAUTES-FRIDMAN (Pr emeritus), Sophie SIBERIL (Dr), Cheng-Ming SUN (Dr), Jean-Luc TEILLAUD (Dr emeritus), Pierre VALIDIRE (Pr).

Aurélie BONI (Tec), Irelka COLINA MORENO (Eng), Solene FASTENACKELS (Eng), Ivo GAMEIRO NATARIO (Eng), Nathalie JOSSEAUME (Tech), Nathalie-Tassadite JUPITER (Tech), Guillaume LACROIX (Eng), Laetitia LACROIX (Eng), Solenne MARMIER (Eng), Carine TORSET (Eng), Yoan VELU (Eng).

Mahmud ANGRINI (PhD student), Nouria BELKACEM (Post-Doc), Bere DIALLO (PhD student), Hélène KAPLON (PhD student), Ioannis KARAGIANNIDIS (Post-Doc), Leila LETAIEFF (PhD student), Florent PETITPREZ) (PhD student).

Administration : Mehdi BENNACI, Esther PEROUMAL

Contact details : 01 44 27 91 00    Email: mehdi.bennaci@crc.jussieu.fr

Selected Publications

  • Fridman WH, Zitvogel L, Sautès-Fridman C, Kroemer G. (2017) The immune contexture in cancer prognosis and treatment. Nat Rev Clin Oncol. 14:717-734. PMID:28741618
  • Giraldo NA, Becht E, Vano Y, Petitprez F, Lacroix L, Validire P, Sanchez-Salas R, Ingels A, Oudard S, Moatti A, Buttard B, Bourass S, Germain C, Cathelineau X, Fridman WH, Sautès-Fridman C. (2017) Tumor-Infiltrating and Peripheral Blood T-cell Immunophenotypes Predict Early Relapse in Localized Clear Cell Renal Cell Carcinoma. Clin Cancer Res. Feb 17. PMID:28213366.
  • Bruhns P, Teillaud JL. (2016) Inhibitory IgG Receptor-Expressing Cells: The Must-Have Accessory for Anti-CD40 Immunomodulatory mAb Efficacy. Cancer Cell. 29(6):771-3. PMID: 27300429.
  • Remark R, Lupo A, Alifano M, Biton J, Ouakrim H, Stefani A, Cremer I, Goc J, Régnard JF, Dieu-Nosjean MC, Damotte D. (2016) Immune contexture and histological response after neoadjuvant chemotherapy predict clinical outcome of lung cancer patients. Oncoimmunology. Dec 8;5(12):e1255394. eCollection 2016. PMID: 28123901
  • Becht E, Giraldo NA, Lacroix L, Buttard B, Elarouci N, Petitprez F, Selves J, Laurent-Puig P, Sautès-Fridman C, Fridman WH, de Reyniès A. (2016) Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression. Genome Biol. 17(1):218. PMID: 27765066.
  • Mansuet-Lupo A, Alifano M, Pécuchet N, Biton J, Becht E, Goc J, Germain C, Ouakrim H, Régnard JF, Cremer I, Laurent-Puig P, Dieu-Nosjean MC, Blons H, Damotte D. (2016) Intra-tumoral Immune Cell Densities are Associated with Lung Adenocarcinoma Gene Alterations. Am J Respir Crit Care Med. Jun 14. PMID: 27299180.
  • Becht E, de Reyniès A, Giraldo NA, Pilati C, Buttard B, Lacroix L, Sèlves J, Sautès-Fridman C, Laurent-Puig P, Fridman WH. (2016) Immune and stromal classification of colorectal cancer is associated with molecular subtypes and relevant for precision immunotherapy. Clin Cancer Res. pii: clincanres.2879. PMID: 26994146.
  • Fucikova J, Becht E, Iribarren K, Goc J, Remark R, Damotte D, Alifano M, Devi P, Biton J, Germain C, Lupo A, Fridman WH, Dieu-Nosjean MC, Kroemer G, Sautes-Fridman C, Cremer I. (2016) Calreticulin expression in human non-small cell lung cancers correlates with increased accumulation of antitumor immune cells and favorable prognosis. Cancer Res. 76 : 1746-56. PMID: 26842877.

Link to PubMed

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