High Levels of Fibrotic Tumor Components Are Associated with Recurrence and Intratumoral Immune Status in Advanced Colorectal Cancer Patients

Overview

Journal Sci Rep

Specialty Science

Date 2024 Dec 27

PMID 39730445

Authors

Gendensuren Dorjkhorloo

Takuya Shiraishi

Bilguun Erkhem-Ochir

Makoto Sohda

Haruka Okami

Arisa Yamaguchi

Ikuma Shioi

Chika Komine

Nobuhiro Nakazawa

Yuta Shibasaki

Takuhisa Okada

Katsuya Osone

Akihiko Sano

Makoto Sakai

Hiroomi Ogawa

Ayaka Katayama

Tetsunari Oyama

Takehiko Yokobori

Ken Shirabe

Hiroshi Saeki

Affiliations

Soon will be listed here.

Abstract

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 surgically resected 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.

References

Deng B, Zhao Z, Kong W, Han C, Shen X, Zhou C . Biological role of matrix stiffness in tumor growth and treatment. J Transl Med. 2022; 20(1):540. PMC: 9682678. DOI: 10.1186/s12967-022-03768-y. View

Peng D, Rodriguez B, Diao L, Chen L, Wang J, Byers L . Collagen promotes anti-PD-1/PD-L1 resistance in cancer through LAIR1-dependent CD8 T cell exhaustion. Nat Commun. 2020; 11(1):4520. PMC: 7481212. DOI: 10.1038/s41467-020-18298-8. View

Dong S, Wang H, Ji H, Hu Y, Zhao S, Yan B . Development and validation of a collagen signature to predict the prognosis of patients with stage II/III colorectal cancer. iScience. 2023; 26(5):106746. PMC: 10192940. DOI: 10.1016/j.isci.2023.106746. View

Kinoshita J, Fushida S, Yamaguchi T, Moriyama H, Saito H, Shimada M . Prognostic value of tumor-infiltrating CD163macrophage in patients with metastatic gastric cancer undergoing multidisciplinary treatment. BMC Cancer. 2022; 22(1):608. PMC: 9166590. DOI: 10.1186/s12885-022-09713-y. View

Akimoto N, Vayrynen J, Zhao M, Ugai T, Fujiyoshi K, Borowsky J . Desmoplastic Reaction, Immune Cell Response, and Prognosis in Colorectal Cancer. Front Immunol. 2022; 13:840198. PMC: 8980356. DOI: 10.3389/fimmu.2022.840198. View

Guo L, Wang C, Qiu X, Pu X, Chang P . Colorectal Cancer Immune Infiltrates: Significance in Patient Prognosis and Immunotherapeutic Efficacy. Front Immunol. 2020; 11:1052. PMC: 7270196. DOI: 10.3389/fimmu.2020.01052. View

Koenig A, Mueller C, Hasel C, Adler G, Menke A . Collagen type I induces disruption of E-cadherin-mediated cell-cell contacts and promotes proliferation of pancreatic carcinoma cells. Cancer Res. 2006; 66(9):4662-71. DOI: 10.1158/0008-5472.CAN-05-2804. View

Maehara J, Masugi Y, Abe T, Tsujikawa H, Kurebayashi Y, Ueno A . Quantification of intratumoral collagen and elastin fibers within hepatocellular carcinoma tissues finds correlations with clinico-patho-radiological features. Hepatol Res. 2019; 50(5):607-619. DOI: 10.1111/hepr.13484. View

Shintani Y, Maeda M, Chaika N, Johnson K, Wheelock M . Collagen I promotes epithelial-to-mesenchymal transition in lung cancer cells via transforming growth factor-beta signaling. Am J Respir Cell Mol Biol. 2007; 38(1):95-104. PMC: 2176131. DOI: 10.1165/rcmb.2007-0071OC. View

10.

Necula L, Matei L, Dragu D, Pitica I, Neagu A, Bleotu C . Collagen Family as Promising Biomarkers and Therapeutic Targets in Cancer. Int J Mol Sci. 2022; 23(20). PMC: 9604126. DOI: 10.3390/ijms232012415. View

11.

Fang M, Yuan J, Peng C, Li Y . Collagen as a double-edged sword in tumor progression. Tumour Biol. 2013; 35(4):2871-82. PMC: 3980040. DOI: 10.1007/s13277-013-1511-7. View

12.

Zhang Y, Zhao Y, Li Q, Wang Y . Macrophages, as a Promising Strategy to Targeted Treatment for Colorectal Cancer Metastasis in Tumor Immune Microenvironment. Front Immunol. 2021; 12:685978. PMC: 8313969. DOI: 10.3389/fimmu.2021.685978. View

13.

Kai F, Drain A, Weaver V . The Extracellular Matrix Modulates the Metastatic Journey. Dev Cell. 2019; 49(3):332-346. PMC: 6527347. DOI: 10.1016/j.devcel.2019.03.026. View

14.

Shiraishi T, Ogawa H, Katayama A, Osone K, Okada T, Enokida Y . Association of tumor size in pathological T4 colorectal cancer with desmoplastic reaction and prognosis. Ann Gastroenterol Surg. 2022; 6(5):667-678. PMC: 9444861. DOI: 10.1002/ags3.12571. View

15.

Larsen A, Kuczek D, Kalvisa A, Siersbaek M, Thorseth M, Johansen A . Collagen Density Modulates the Immunosuppressive Functions of Macrophages. J Immunol. 2020; 205(5):1461-1472. DOI: 10.4049/jimmunol.1900789. View

16.

Gilles C, Polette M, Seiki M, Birembaut P, Thompson E . Implication of collagen type I-induced membrane-type 1-matrix metalloproteinase expression and matrix metalloproteinase-2 activation in the metastatic progression of breast carcinoma. Lab Invest. 1997; 76(5):651-60. View

17.

Rygiel T, Stolte E, de Ruiter T, van de Weijer M, Meyaard L . Tumor-expressed collagens can modulate immune cell function through the inhibitory collagen receptor LAIR-1. Mol Immunol. 2011; 49(1-2):402-6. DOI: 10.1016/j.molimm.2011.09.006. View

18.

Chen Y, Yang S, Tavormina J, Tampe D, Zeisberg M, Wang H . Oncogenic collagen I homotrimers from cancer cells bind to α3β1 integrin and impact tumor microbiome and immunity to promote pancreatic cancer. Cancer Cell. 2022; 40(8):818-834.e9. PMC: 9831277. DOI: 10.1016/j.ccell.2022.06.011. View

19.

Song K, Yu Z, Zu X, Li G, Hu Z, Xue Y . Collagen Remodeling along Cancer Progression Providing a Novel Opportunity for Cancer Diagnosis and Treatment. Int J Mol Sci. 2022; 23(18). PMC: 9502421. DOI: 10.3390/ijms231810509. View

20.

De Martino D, Bravo-Cordero J . Collagens in Cancer: Structural Regulators and Guardians of Cancer Progression. Cancer Res. 2023; 83(9):1386-1392. PMC: 10159947. DOI: 10.1158/0008-5472.CAN-22-2034. View