Abstract
Significant advances have been made towards understanding the role of immune cell-tumor interplay in either suppressing or promoting tumor growth, progression, and recurrence, however, the roles of additional stromal elements, cell types and/or cell states remain ill-defined. The overarching goal of this NCI-sponsored workshop was to highlight and integrate the critical functions of non-immune stromal components in regulating tumor heterogeneity and its impact on tumor initiation, progression, and resistance to therapy. The workshop explored the opposing roles of tumor supportive versus suppressive stroma and how cellular composition and function may be altered during disease progression. It also highlighted microenvironment-centered mechanisms dictating indolence or aggressiveness of early lesions and how spatial geography impacts stromal attributes and function. The prognostic and therapeutic implications as well as potential vulnerabilities within the heterogeneous tumor microenvironment were also discussed. These broad topics were included in this workshop as an effort to identify current challenges and knowledge gaps in the field.
Highlights
The last two decades have seen significant gains in unveiling the crosstalk between cancer cells and the stroma within which they reside
Many aspects of the biological alterations that arise in stromal cell types or in the extracellular matrix components that may drive cancer initiation or progression remain poorly understood
While most studies involving circulating tumor cells (CTCs) use cytokeratin+CD45- as the schema for detecting CTCs, Wong’s group discovered that hybrid cells that are cytokeratin+CD45+ make up more than 90% of circulating cancer cells [32]. This discovery suggests that fusogenic events between CD45- epithelial cells and CD45+ macrophages are at play in the tumor microenvironment (TME) in addition to more widely appreciated cell-cell interactions and that these events may impact tumor progression
Summary
Renee E. Vickman1,*, Douglas V. Faget2,*, Philip Beachy3, David Beebe4, Neil A. Bhowmick5, Edna Cukierman6, Wu-Min Deng7, James G. Granneman8, Jeffrey Hildesheim9, Raghu Kalluri10, Ken S. Lau11, Ernst Lengyel12, Joakim Lundeberg13, Jorge Moscat14, Peter S. Nelson15, Kristian Pietras16, Katerina Politi17, Ellen Puré18, Ruth Scherz-Shouval19, Mara H. Sherman20, David Tuveson21, Ashani T. Weeraratna22, Richard M. White23, Melissa H. Wong20, Elisa C. Woodhouse9, Ying Zheng24, Simon W. Hayward1,# and Sheila A. Stewart2,# Keywords: tumor microenvironment; stromal heterogeneity; extracellular matrix; cellular plasticity; therapy resistance
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