公开(公告)号：US20180100201A1

公开(公告)日：2018-04-12

申请号：US15844601

申请日：2017-12-17

申请人： The Broad Institute Inc. ,  Massachusetts Institute of Technology ,  Dana-Farber Cancer Institute, Inc. ,  The General Hospital Corporation

发明人： Levi A. Garraway ,  Benjamin Izar ,  Sanjay Prakadan ,  Aviv Regev ,  Orit Rozenblatt-Rosen ,  Alexander K. Shalek ,  Mario Suva ,  Itay Tirosh ,  Andrew Venteicher ,  Marc H. Wadsworth II ,  Bradley Bernstein ,  Anuraag Parikh ,  Sidharth Puram

IPC分类号： C12Q1/6886

CPC分类号： C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/112 ,  C12Q2600/158

摘要： This invention relates generally to compositions and methods for identifying genes and gene networks that respond to, modulate, control or otherwise influence tumors and tissues, including cells and cell types of the tumors and tissues, and malignant, microenvironmental, or immunologic states of the tumor cells and tissues. The invention also relates to methods of diagnosing, prognosing and/or staging of tumors, tissues and cells, and provides compositions and methods of modulating expression of genes and gene networks of tumors, tissues and cells, as well as methods of identifying, designing and selecting appropriate treatment regimens. The invention also relates to the modulation of complement activity to shift cellular immunity and obtain an effective therapeutic response.

公开(公告)号：US20200071773A1

公开(公告)日：2020-03-05

申请号：US16604651

申请日：2018-04-12

申请人： Massachusetts Eye and Ear Infirmary ,  The General Hospital Corporation ,  The Broad Institute, Inc. ,  Massachusetts Institute of Technology

发明人： Sidharth Puram ,  Itay Tirosh ,  Anuraag Parikh ,  Derrick Lin ,  Aviv Regev ,  Bradley Bernstein

IPC分类号： C12Q1/6886 ,  A61P35/04 ,  C12Q1/6837 ,  G16B25/10 ,  G16B40/00

摘要： The present invention advantageously provides for novel gene signatures, tools and methods for the treatment and prognosis of epithelial tumors. Applicants have used single cell RNA-seq to reveal novel expression programs of malignant, stromal and immune cells in the HNSCC tumor ecosystem. Malignant cells varied in expression of programs related to stress, hypoxia and epithelial differentiation. A partial EMT-like program (p-EMT) was discovered that was expressed in cells residing at the leading edge of tumors. Applicants unexpectedly linked the p-EMT state to metastasis and adverse clinical features that may be used to direct treatment of epithelial cancers (e.g., HNSCC). Applicants also show that metastases are dynamically regulated by the tumor microenvironment (TME). Finally, a computational modeling approach was developed that allows analysis of malignant cells in bulk sequencing samples.