High levels of fibrotic tumor components are associated with recurrence and intratumoral immune status in advanced colorectal cancer patients

Sep 21, 2026

Study of advanced colorectal cancer patients investigates how tumor fibrosis relates to immune status and clinical outcomes. Collagen and elastin deposition were quantified using elastic van Gieson (EVG) staining, while immune cell markers CD3, CD8, CD86, and CD163 were assessed in surgically resected primary tumors from 78 pT4 cases. High collagen, elastin, and EVG scores correlated with aggressive features and shorter disease-free survival, with high EVG scoring independently predicting poor outcomes. Tumors with high collagen and EVG scores showed reduced intratumoral CD3+ and CD8+ cell infiltration, suggesting EVG-based fibrosis assessment as a practical predictor of recurrence in immune-tolerant high-risk patients.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Background

ECM disruption and fibrosis in tumor progression

Fibrosis-driven modulation of the immune environment

Methods

EVG histochemical assessment of collagen and elastin

Immunohistochemistry for immune markers

Results

Associations with aggressive features and disease-free survival

EVG as an independent predictor

Links between high fibrosis scores and reduced T-cell markers

Implications

EVG fibrosis evaluation as a recurrence predictor

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN High levels offibrotic tumor components are associated with recurrence and intratumoral immune status in advanced colorectal cancer patients Gendensuren Dorjkhorloo1,4, Takuya Shiraishi1,4, Bilguun Erkhem-Ochir2, Makoto Sohda1􀀍, Haruka Okami1, Arisa Yamaguchi1, Ikuma Shioi1, Chika Komine1, Nobuhiro Nakazawa1, Yuta Shibasaki1, Takuhisa Okada1, Katsuya Osone1, Akihiko Sano1, Makoto Sakai1, Hiroomi Ogawa1, Ayaka Katayama3, Tetsunari Oyama3, Takehiko Yokobori2􀀍, Ken Shirabe1 & Hiroshi Saeki1 The importance of collagen and elastin remains incompletely understood concerning tumor immunity in cancer tissues. This study explored the clinical significance of collagen and elastin deposition on tumor immunity in advanced colorectal cancer patients. The collagen and elastin contents were assessed simultaneously using elastic van Gieson (EVG) histochemical staining. Immunohistochemical staining was performed to measure the immune cell markers CD3, CD8, CD86, and CD163 in surgicallyresected primary tumors from 78 pT4 colorectal cancer patients. High collagen, elastin, and EVG scores are associated with aggressive characteristics and short disease-free survival. A high EVG score was identified as an independent predictor of poor disease-free survival. Furthermore, tumors with high collagen and EVG scores exhibited significantly fewer intratumoral CD3 +and CD8 +cells. Evaluating tumor fibrosis using the classical and straightforward EVG staining method could be a reliable predictor of recurrence in high-risk colorectal cancer patients with tumor immune tolerance. Keywords Tumor fibrosis, Collagen, Elastin, Immune cell infiltration, Locally advanced colon cancer Tumor progression involves substantial disruption of the extracellular matrix (ECM)1,2. Cancer cells exhibit increased ECM stiffness and fibrosis in the early phases. Eventually, the remodeled environment becomes crucial for tumor progression and treatment resistance in advanced phases3,4. Augmented fibrotic ECM has been correlated with treatment resistance, epithelial–mesenchymal transition (EMT), which is related to cancer aggressiveness, and poor prognosis in various cancer types5–8. In addition to promoting tumor growth and survival, tumor fibrosis strongly influences the immune environment in cancer9, 10. The importance of immune cell infiltration in prognosis and treatment response has been extensively studied11, 12. In numerous cancer types, increased densities of tumor-infiltrating lymphocytes (TILs) are reportedly correlated with enhanced survival rates and heightened responsiveness to anticancer treatment regimens13–16. In contrast, different studies have reported different conclusions regarding macrophages, such as alternatively activated M2 macrophages17, 18. M2-type macrophages exert tumor-promoting effects through increased TGF-β signaling, which eventually contributes to EMT and the activation of cancer-associated fibroblasts19,20. Thus, the importance of the immune system in the tumor microenvironment (TME) as both asuppressive factor and a tumor-promoting factor has been established. 1Department of General Surgical Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. 2Research Program for Omics-based Medical Science, Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research (GIAR), 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. 3Department of Diagnostic Pathology, Graduate School of Medicine, Gunma University, Maebashi, Japan. 4Gendensuren Dorjkhorloo and Takuya Shiraishi contributed equally to this work. 􀀍 email: [msohda@gunma-u.ac.jp](msohda@gunma-u.ac.jp); [bori45@gunma-u.ac.jp](bori45@gunma-u.ac.jp) [www. nature.com/scientificreports/](www. nature.com/scientificreports/) CD86 is a macrophage marker indicating macrophages’ presence regardless of their activation state. It p

FAQs

How were collagen and elastin levels in tumors assessed in the study?

Collagen and elastin contents were evaluated simultaneously using elastic van Gieson (EVG) histochemical staining, followed by quantitative image analysis of fibrotic areas.

Which immune cell markers were measured to reflect intratumoral immune status?

The study measured CD3, CD8, CD86, and CD163 using immunohistochemical staining on surgically resected primary tumors.

What clinical outcome associations were found for high collagen and EVG scores?

High collagen, elastin, and EVG scores were linked to aggressive tumor characteristics and shorter disease-free survival, and a high EVG score independently predicted poorer disease-free survival.

Sep 21, 2026

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