Quantitative characterization of CD8+ T cell clustering and spatial heterogeneity in solid tumors

Chang Gong, Robert A Anders, Qingfeng Zhu, Janis M Taube, Benjamin Green, Wenting Cheng, Imke H. Bartelink, Paolo Vicini, Bing Wang, Aleksander S Popel

Research output: Contribution to journalArticle

Abstract

Quantitative characterization of the tumor microenvironment, including its immuno-architecture, is important for developing quantitative diagnostic and predictive biomarkers, matching patients to the most appropriate treatments for precision medicine, and for providing quantitative data for building systems biology computational models able to predict tumor dynamics in the context of immune checkpoint blockade therapies. The intra- and inter-tumoral spatial heterogeneities are potentially key to the understanding of the dose-response relationships, but they also bring challenges to properly parameterizing and validating such models. In this study, we developed a workflow to detect CD8+ T cells from whole slide imaging data, and quantify the spatial heterogeneity using multiple metrics by applying spatial point pattern analysis and morphometric analysis. The results indicate a higher intra-tumoral heterogeneity compared with the heterogeneity across patients. By comparing the baseline metrics with PD-1 blockade treatment outcome, our results indicate that the number of high-density T cell clusters of both circular and elongated shapes are higher in patients who responded to the treatment. This methodology can be applied to quantitatively characterize the tumor microenvironment, including immuno-architecture, and its heterogeneity for different cancer types.

Original languageEnglish (US)
Article number00649
JournalFrontiers in Oncology
Volume9
Issue numberJAN
DOIs
StatePublished - Jan 1 2019

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Cluster Analysis
Tumor Microenvironment
T-Lymphocytes
Neoplasms
Precision Medicine
Systems Biology
Workflow
Information Systems
Therapeutics
Biomarkers

Keywords

  • Digital pathology
  • Immuno-architecture
  • Spatial patterns
  • Spatial statistics
  • Systems biology

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Quantitative characterization of CD8+ T cell clustering and spatial heterogeneity in solid tumors. / Gong, Chang; Anders, Robert A; Zhu, Qingfeng; Taube, Janis M; Green, Benjamin; Cheng, Wenting; Bartelink, Imke H.; Vicini, Paolo; Wang, Bing; Popel, Aleksander S.

In: Frontiers in Oncology, Vol. 9, No. JAN, 00649, 01.01.2019.

Research output: Contribution to journalArticle

Gong, Chang ; Anders, Robert A ; Zhu, Qingfeng ; Taube, Janis M ; Green, Benjamin ; Cheng, Wenting ; Bartelink, Imke H. ; Vicini, Paolo ; Wang, Bing ; Popel, Aleksander S. / Quantitative characterization of CD8+ T cell clustering and spatial heterogeneity in solid tumors. In: Frontiers in Oncology. 2019 ; Vol. 9, No. JAN.
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