Our main research interest is to gain a deep understanding of the tumor-intrinsic and extrinsic mechanisms that promote or dampen anti-tumor T cell immunity.
- We gain a deep understanding of the molecular states of human TILs (tumor infiltrating lymphocytes) and the tumor microenvironment at stages of tumor escape or tumor rejection using systems approaches. We study tumors at the steady state but also following T cell therapy and other immunotherapies.
- We unveil fundamental molecular mechanisms driving T cell dysfunction in tumors at the steady state.
- We characterize tumor and stroma-driven exclusion mechanisms of TILs.
- We define how genomic alterations (ie homologous recombination repair deficiency, HRD) and tumor heterogeneity regulate TIL inflammation status of tumors.
The lab employs orthogonal approaches to discovery, including single cell proteomic, transcriptional and epigenetic interrogation, advanced high dimensional microscopy, topologically referenced transcriptional profiling, 3D tumor organoids and histocultures, mouse models and computational tools.
- Dangaj D, Bruand M, Grimm AJ, Ronet C, Barras D, Duttagupta PA, Lanitis E, Duraiswamy J, Tanyi JL, Benencia F, Conejo-Garcia J, Ramay HR, Montone KT, Powell DJ Jr, Gimotty PA, Facciabene A, Jackson DG, Weber JS, Rodig SJ, Hodi SF, Kandalaft LE, Irving M, Zhang L, Foukas P, Rusakiewicz S, Delorenzi M, Coukos G. Cooperation between Constitutive and Inducible Chemokines Enables T Cell Engraftment and Immune Attack in Solid Tumors. Cancer Cell. 2019 Jun 10;35(6):885-900.e10. doi: 10.1016/j.ccell.2019.05.004.
- Dangaj D*, Barras D*, Coukos G. Tumor Landscapes: β-Catenin Drives Immune Desertification. Clin Cancer Res. 2019 May 15;25(10):2943-2945. doi: 10.1158/1078-0432.
- Bobisse S, Genolet R, Roberti A, Tanyi JL, Racle J, Stevenson BJ, Iseli C, Michel A, Le Bitoux MA, Guillaume P, Schmidt J, Bianchi V, Dangaj D, Fenwick C, Derré L, Xenarios I, Michielin O, Romero P, Monos DS, Zoete V, Gfeller D, Kandalaft LE, Coukos G, Harari A. Sensitive and frequent identification of high avidity neo-epitope specific CD8 + T cells in immunotherapy-naive ovarian cancer. Nat Commun. 2018 Mar 15;9(1):1092. doi: 10.1038/s41467-018-03301-0.
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