Digital analysis and epigenetic regulation of the signature of rejection in colorectal cancer

Oncoimmunology
Viktor H KoelzerAlessandro Lugli

Abstract

The immune system plays a pivotal role in the development and progression of colorectal cancer (CRC). Tumor immune rejection has been previously linked to the activation of the interferon-stimulated genes (ISG) STAT1, IRF-5 and IRF-1. Specific immunoregulatory microRNAs (miRNAs) may impact the expression of these ISG in the tumor microenvironment. In this translational study, we develop a digital image analysis protocol to identify the ISG-gene expression signature and investigate miRNA expression in the immediate environment of invading cancer cells. Digital immunophenotyping was performed using next generation tissue microarrays from 241 well-characterized CRC patients and analyzed with clinicopathological and molecular information. Active ISG signaling in the tumor stroma differentiated an immune-activated (n = 178) and a quiescent (n = 43) phenotype. The activated phenotype was associated with high counts of intratumoral CD8+ cytotoxic T-lymphocytes (CTL; p = 0.007) and expression of the immune effector molecules granzyme B (p < 0.001) and perforin (p = 0.020). Immune-activated tumors also showed an elevated expression of the intercellular adhesion molecule-1 (ICAM-1, p = 0.006) which may facilitate CTL infiltration. Patien...Continue Reading

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Citations

Dec 2, 2017·Oncotarget·Yuan-Ke LiangDe Zeng
Nov 25, 2018·Virchows Archiv : an International Journal of Pathology·Viktor H KoelzerKirsten D Mertz
Apr 21, 2020·OncoTargets and Therapy·Jiehong Kong, Weipeng Wang
Jan 11, 2020·Journal of Pathology Informatics·Stefan ZahndInti Zlobec
Mar 19, 2021·Frontiers in Cell and Developmental Biology·Rui MaoTongtong Zhang
Apr 13, 2019·Clinical Oncology : a Journal of the Royal College of Radiologists·S M O'Cathail, F M Buffa

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