Journal
CANCER CELL
Volume 40, Issue 11, Pages 1423-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2022.09.014
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Funding
- EMBO postdoctoral fellowship [ALTF*300-2017]
- Tobacco-Related Disease Research Program [T30FT0824]
- Stanford Dean's Fellowship and the Leukemia & Lymphoma Society CDP
- Stanford Graduate Fellowship in Science and Engineering
- National Institute of Health [CA217450, CA231997, 3U54HG010426, 5U54CA209971, 3U19AI100627, 5U2CCA233195, U19AI057229, 1U2CCA233238]
- Food and Drug Administration [HHSF223201610018C]
- Cancer Research UK [C27165/A29073]
- Bill and Melinda Gates Foundation [OPP1113682]
- Cancer Research Institute
- Parker Institute for Cancer Immunotherapy
- Kenneth Rainin Foundation [2018-575]
- Celgene, Inc. [133826, 134073]
- Rachford & Carlotta A. Harris Endowed Chair
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Intratumoral heterogeneity is a critical feature of tumor progression and treatment response. Current technologies are limited in accurately tracking phenotypes and clonal evolution within tumors. This study developed a new imaging technique that can track barcodes within tissue, providing insights into the intratumoral heterogeneity.
Intratumoral heterogeneity is a seminal feature of human tumors contributing to tumor progression and response to treatment. Current technologies are still largely unsuitable to accurately track phenotypes and clonal evolution within tumors, especially in response to genetic manipulations. Here, we developed epitopes for imaging using combinatorial tagging (EpicTags), which we coupled to multiplexed ion beam imaging (EpicMIBI) for in situ tracking of barcodes within tissue microenvironments. Using EpicMIBI, we dissected the spatial component of cell lineages and phenotypes in xenograft models of small cell lung cancer. We observed emergent properties from mixed clones leading to the preferential expansion of clonal patches for both neuroendocrine and non-neuroendocrine cancer cell states in these models. In a tumor model harboring a fraction of PTEN-deficient cancer cells, we observed a non-autonomous increase of clonal patch size in PTEN wild-type cancer cells. EpicMIBI facilitates in situ interrogation of cell-intrinsic and cell-extrinsic processes involved in intratumoral heterogeneity.
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