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Spatial epitope barcoding reveals clonal tumor patch behaviors.

Xavier Rovira-Clavé1, Alexandros P Drainas2, Sizun Jiang3

  • 1Department of Pathology, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.

Cancer Cell
|October 14, 2022
PubMed
Summary
This summary is machine-generated.

New imaging technology, Epitopes for Imaging using Combinatorial Tagging (EpicTags) coupled with Multiplexed Ion Beam Imaging (EpicMIBI), tracks tumor cell evolution. This method reveals how mixed cancer cell populations grow and interact within tumors.

Keywords:
MIBIPTENSCLCmultiplex imagingneuroendocrinespatial barcodingtumor heterogeneity

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Area of Science:

  • Oncology
  • Molecular Biology
  • Biotechnology

Background:

  • Intratumoral heterogeneity is a key factor in tumor progression and treatment resistance.
  • Existing technologies struggle to track cellular phenotypes and clonal evolution within tumors, especially after genetic alterations.
  • Understanding spatial dynamics of tumor cells is crucial for developing effective cancer therapies.

Purpose of the Study:

  • To develop and validate a novel imaging technique for in situ tracking of cellular phenotypes and clonal evolution within tumors.
  • To investigate the spatial organization and clonal dynamics in small cell lung cancer xenograft models.
  • To analyze cell-intrinsic and cell-extrinsic factors contributing to intratumoral heterogeneity.

Main Methods:

  • Development of epitopes for imaging using combinatorial tagging (EpicTags).
  • Coupling EpicTags with multiplexed ion beam imaging (EpicMIBI) for high-resolution spatial analysis.
  • Application of EpicMIBI to xenograft models of small cell lung cancer to track cell lineages and phenotypes.

Main Results:

  • EpicMIBI successfully enabled in situ tracking of barcodes within tumor microenvironments.
  • Observed preferential expansion of clonal patches comprising both neuroendocrine and non-neuroendocrine cancer cell states in mixed clones.
  • Demonstrated a non-autonomous increase in PTEN wild-type cancer cell patch size when PTEN-deficient cells were present.

Conclusions:

  • EpicMIBI is a powerful tool for dissecting the spatial component of intratumoral heterogeneity.
  • The study provides insights into emergent properties of mixed clones and their impact on tumor growth.
  • This technology facilitates the interrogation of cell-intrinsic and cell-extrinsic processes driving tumor evolution.