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Deconstructing tumor heterogeneity: the stromal perspective


Vickman RERenee E , Faget DVDouglas V , Beachy PPhilip , Beebe DDavid , Bhowmick NANeil A , Cukierman EEdna , Deng WMWu-Min , Granneman JGJames G , Hildesheim JJeffrey , Kalluri RRaghu , Lau KSKen S , Lengyel EErnst , Lundeberg JJoakim , Moscat JJorge , Nelson PSPeter S , Pietras KKristian , Politi KKaterina , Puré EEllen , Scherz-Shouval RRuth , Sherman MHMara H , Tuveson DDavid , Weeraratna ATAshani T , White RMRichard M , Wong MHMelissa H , Woodhouse ECElisa C , Zheng YYing , Hayward SWSimon W , Stewart SASheila A . Oncotarget. 2020 10 6; 11(40). 3621-3632


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 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.