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The Tumor Microenvironment

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...

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Establishment of a Co-culture System of Patient-Derived Colorectal Tumor Organoids and Tumor-Infiltrating Lymphocytes (TILs)

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Epigenetic Modulation, Intratumoral Microbiome, and Immunity in Early-Onset Colorectal Cancer.

Ning Jin¹, Rebecca Hoyd¹, Ayse S Yilmaz²

¹Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.

Cancer Research Communications

|October 24, 2025

Summary

Early-onset colorectal cancer (EOCRC) shows accelerated epigenetic aging and altered immune responses. Environmental factors may drive these changes, contributing to increased EOCRC incidence in young adults.

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Published on: March 10, 2015

Area of Science:

Oncology
Epigenetics
Immunology

Background:

Colorectal cancer incidence is rising in young adults (<50 years).
The causes of early-onset colorectal cancer (EOCRC) are largely unknown, despite germline mutations in ~20% of cases.
Nongenetic factors like environment and lifestyle are suspected contributors to sporadic EOCRC.

Purpose of the Study:

To investigate the role of epigenetics, microbiome, and immunome in EOCRC.
To identify molecular signatures associated with EOCRC development.
To explore the link between environmental factors and EOCRC etiology.

Main Methods:

DNA methylation (DNAm) signature and DNAm age analysis in EOCRC using The Cancer Genome Atlas (TCGA).
Intratumoral microbe identification from TCGA and Oncology Research Information Exchange Network (ORIEN) datasets.
Correlation analysis between microbes and deconvolved immune cell abundances in EOCRC.

Main Results:

EOCRC tumors exhibited an epigenetic age 12 years older than average-onset colorectal cancer (AOCRC) tumors.
Differentially methylated sites were linked to cAMP signaling, G protein-coupled receptor signaling, phagosome formation, and S100 signaling.
While no consistent microbial differences were found, EOCRC tumors showed stronger microbe-immune interactions, suggesting immune dysregulation.

Conclusions:

Accelerated epigenetic aging and epigenetic modulation are key factors in EOCRC development.
Altered immune responses and chronic inflammation may contribute to EOCRC pathogenesis.
Environmentally driven factors likely influence EOCRC through epigenetic and immune system alterations.