Analysis of Spatial Organization of Suppressive Myeloid Cells and Effector T Cells in Colorectal Cancer-A Potential Tool for Discovering Prognostic Biomarkers in Clinical Research.

Frontiers in Immunology
Natalie ZwingKonstanty Korski

Abstract

The development and progression of solid tumors such as colorectal cancer (CRC) are known to be affected by the immune system and cell types such as T cells, natural killer (NK) cells, and natural killer T (NKT) cells are emerging as interesting targets for immunotherapy and clinical biomarker research. In addition, CD3+ and CD8+ T cell distribution in tumors has shown positive prognostic value in stage I-III CRC. Recent developments in digital computational pathology support not only classical cell density based tumor characterization, but also a more comprehensive analysis of the spatial cell organization in the tumor immune microenvironment (TiME). Leveraging that methodology in the current study, we tried to address the question of how the distribution of myeloid derived suppressor cells in TiME of primary CRC affects the function and location of cytotoxic T cells. We applied multicolored immunohistochemistry to identify monocytic (CD11b+CD14+) and granulocytic (CD11b+CD15+) myeloid cell populations together with proliferating and non-proliferating cytotoxic T cells (CD8+Ki67+/-). Through automated object detection and image registration using HALO software (IndicaLabs), we applied dedicated spatial statistics to measure th...Continue Reading

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Methods Mentioned

BETA
RNAseq

Software Mentioned

GAD
NEXES
R package spatstat
TiME
BioQC
GGplot2
HALO
LRpath
DESeq2

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