Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 1/2015

01-01-2015 | Research Article

Interleukin-17 is a favorable prognostic marker for colorectal cancer

Authors: Y. Lin, J. Xu, H. Su, W. Zhong, Y. Yuan, Z. Yu, Y. Fang, H. Zhou, C. Li, K. Huang

Published in: Clinical and Translational Oncology | Issue 1/2015

Login to get access

Abstract

Purpose

The role of interleukin-17 (IL-17) in the tumor microenvironment is controversial. We analyzed the in situ tumor expression of IL-17 in colorectal cancer (CRC), adenoma and non-tumor tissue to explore the possible correlation of IL-17 expression to clinicopathological characteristics, tumor-infiltrating neutrophils (TINs) and survival in CRC.

Methods

We reviewed the records of 78 consecutive patients diagnosed with CRC. Archival tissues were used. Thirty-six patients with colorectal adenoma were also included. From the 78 CRC patients, we randomly chose 40 cases and collected non-tumor tissue at 10 cm from the edge of the resected tumor. Immunohistochemistry was performed using anti-IL-17 and anti-CD15 (targeting neutrophils) antibody, respectively. Real-time PCR was used to detect IL-17 mRNA in different tissues. Associations between IL-17 expression, clinicopathological parameters and prognosis were evaluated.

Results

The level of IL-17 mRNA was higher in CRC than in adenoma and non-tumor tissue (P < 0.05). Positive IL-17 protein expression was observed more frequently in CRC as compared to colorectal adenoma and non-tumor tissue, respectively (P < 0.01). IL-17 expression correlated to well differentiation and early stage CRC. The number of CD15+ neutrophils significantly increased in CRC and positively correlated to the expression of IL-17 (P < 0.05). Both Kaplan–Meier analysis and multivariate Cox regression analysis indicated that patients with positive IL-17 expression showed better overall survival.

Conclusions

The association between IL-17 expression and the clinicopathological parameters, as well as the clinical outcome suggests a significant role of IL-17 in CRC. IL-17 is a marker of favorable prognosis.
Literature
1.
Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454:436–44.PubMedCrossRef
2.
Pikarsky E, Porat RM, Stein I, Abramovitch R, Amit S, Kasem S, et al. NF-kappaB functions as a tumour promoter in inflammation-associated cancer. Nature. 2004;431:461–6.PubMedCrossRef
3.
Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313:1960–4.PubMedCrossRef
4.
Cui G, Yuan A, Goll R, Florholmen J. IL-17A in the tumor microenvironment of the human colorectal adenoma–carcinoma sequence. Scand J Gastroenterol. 2012;47:1304–12.PubMedCrossRef
5.
Le Gouvello S, Bastuji-Garin S, Aloulou N, Mansour H, Chaumette MT, Berrehar F, et al. High prevalence of Foxp3 and IL17 in MMR-proficient colorectal carcinomas. Gut. 2008;57:772–9.PubMedCrossRef
6.
Zhang JP, Yan J, Xu J, Pang XH, Chen MS, Li L, et al. Increased intratumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients. J Hepatol. 2009;50:980–9.PubMedCrossRef
7.
Olsen T, Rismo R, Cui G, Goll R, Christiansen I, Florholmen J. TH1 and TH17 interactions in untreated inflamed mucosa of inflammatory bowel disease, and their potential to mediate the inflammation. Cytokine. 2011;56:633–40.PubMedCrossRef
8.
Petanidis S, Anestakis D, Argyraki M, Hadzopoulou-Cladaras M, Salifoglou A. Differential expression of il-17, 22 and 23 in the progression of colorectal cancer in patients with k-ras mutation: ras signal inhibition and crosstalk with GM-CSF and IFN-gamma. PLoS One. 2013;8:e73616.PubMedCentralPubMedCrossRef
9.
10.
Martin-Orozco N, Muranski P, Chung Y, Yang XO, Yamazaki T, Lu S, et al. T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity. 2009;31:787–98.PubMedCentralPubMedCrossRef
11.
Muranski P, Boni A, Antony PA, Cassard L, Irvine KR, Kaiser A, et al. Tumor-specific Th17-polarized cells eradicate large established melanoma. Blood. 2008;112:362–73.PubMedCentralPubMedCrossRef
12.
He D, Li H, Yusuf N, Elmets CA, Li J, Mountz JD, et al. IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells. J Immunol. 2010;184:2281–8.PubMedCentralPubMedCrossRef
13.
Tosolini M, Kirilovsky A, Mlecnik B, Fredriksen T, Mauger S, Bindea G, et al. Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res. 2011;71:1263–71.PubMedCrossRef
14.
Wakita D, Sumida K, Iwakura Y, Nishikawa H, Ohkuri T, Chamoto K, et al. Tumor-infiltrating IL-17-producing gammadelta T cells support the progression of tumor by promoting angiogenesis. Eur J Immunol. 2010;40:1927–37.PubMedCrossRef
15.
16.
Kuang DM, Zhao Q, Wu Y, Peng C, Wang J, Xu Z, et al. Peritumoral neutrophils link inflammatory response to disease progression by fostering angiogenesis in hepatocellular carcinoma. J Hepatol. 2011;54:948–55.PubMedCrossRef
17.
Zhao JJ, Pan K, Wang W, Chen JG, Wu YH, Lv L, et al. The prognostic value of tumor-infiltrating neutrophils in gastric adenocarcinoma after resection. PLoS One. 2012;7:e33655.PubMedCentralPubMedCrossRef
18.
Lin Y, Buckhaults PJ, Lee JR, Xiong H, Farrell C, Podolsky RH, et al. Association of the actin-binding protein transgelin with lymph node metastasis in human colorectal cancer. Neoplasia. 2009;11:864–73.PubMedCentralPubMed
19.
Mazumdar M, Glassman JR. Categorizing a prognostic variable: review of methods, code for easy implementation and applications to decision-making about cancer treatments. Stat Med. 2000;19:113–32.PubMedCrossRef
20.
Bettelli E, Korn T, Oukka M, Kuchroo VK. Induction and effector functions of T(H)17 cells. Nature. 2008;453:1051–7.PubMedCrossRef
21.
Nieminen U, Jussila A, Nordling S, Mustonen H, Farkkila MA. Inflammation and disease duration have a cumulative effect on the risk of dysplasia and carcinoma in IBD: a case–control observational study based on registry data. Int J Cancer. 2014;134(1):189–96.PubMedCrossRef
22.
Rubin DT, Huo D, Kinnucan JA, Sedrak MS, McCullom NE, Bunnag AP, et al. Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis: a case–control study. Clin Gastroenterol Hepatol. 2013;11(12):1601–8.PubMedCrossRef
23.
Liu J, Duan Y, Cheng X, Chen X, Xie W, Long H, et al. IL-17 is associated with poor prognosis and promotes angiogenesis via stimulating VEGF production of cancer cells in colorectal carcinoma. Biochem Biophys Res Commun. 2011;407:348–54.PubMedCrossRef
24.
Lan C, Huang X, Lin S, Huang H, Cai Q, Lu J, et al. High density of IL-17-producing cells is associated with improved prognosis for advanced epithelial ovarian cancer. Cell Tissue Res. 2013;352:351–9.PubMedCrossRef
25.
Clark RA, Klebanoff SJ. Neutrophil-mediated tumor cell cytotoxicity: role of the peroxidase system. J Exp Med. 1975;141:1442–7.PubMedCrossRef
26.
Colombo MP, Ferrari G, Stoppacciaro A, Parenza M, Rodolfo M, Mavilio F, et al. Granulocyte colony-stimulating factor gene transfer suppresses tumorigenicity of a murine adenocarcinoma in vivo. J Exp Med. 1991;173:889–97.PubMedCrossRef
27.
Granot Z, Henke E, Comen EA, King TA, Norton L, Benezra R. Tumor entrained neutrophils inhibit seeding in the premetastatic lung. Cancer Cell. 2011;20:300–14.PubMedCentralPubMedCrossRef
28.
Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, et al. Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell. 2009;16:183–94.PubMedCentralPubMedCrossRef
29.
Droeser RA, Hirt C, Eppenberger-Castori S, Zlobec I, Viehl CT, Frey DM, et al. High myeloperoxidase positive cell infiltration in colorectal cancer is an independent favorable prognostic factor. PLoS One. 2013;8:e64814.PubMedCentralPubMedCrossRef
30.
Ilie M, Hofman V, Ortholan C, Bonnetaud C, Coelle C, Mouroux J, et al. Predictive clinical outcome of the intratumoral CD66b-positive neutrophil-to-CD8-positive T-cell ratio in patients with resectable nonsmall cell lung cancer. Cancer. 2012;118:1726–37.PubMedCrossRef
31.
Jensen HK, Donskov F, Marcussen N, Nordsmark M, Lundbeck F, von der Maase H. Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma. J Clin Oncol. 2009;27:4709–17.PubMedCrossRef
32.
Li YW, Qiu SJ, Fan J, Zhou J, Gao Q, Xiao YS, et al. Intratumoral neutrophils: a poor prognostic factor for hepatocellular carcinoma following resection. J Hepatol. 2011;54:497–505.PubMedCrossRef
33.
Rao HL, Chen JW, Li M, Xiao YB, Fu J, Zeng YX, et al. Increased intratumoral neutrophil in colorectal carcinomas correlates closely with malignant phenotype and predicts patients’ adverse prognosis. PLoS One. 2012;7:e30806.PubMedCentralPubMedCrossRef
Metadata
Title
Interleukin-17 is a favorable prognostic marker for colorectal cancer
Authors
Y. Lin
J. Xu
H. Su
W. Zhong
Y. Yuan
Z. Yu
Y. Fang
H. Zhou
C. Li
K. Huang
Publication date
01-01-2015
Publisher
Springer Milan
Published in
Clinical and Translational Oncology / Issue 1/2015
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-014-1197-3

Other articles of this Issue 1/2015

Clinical and Translational Oncology 1/2015 Go to the issue

Brief Research Article

MiR-215/192 participates in gastric cancer progression

Correspondence

Indirect comparisons in cost-effectiveness analysis: are we being naïve?

Research Article

Cost-effectiveness analysis of pazopanib in second-line treatment of advanced soft tissue sarcoma in Spain

Acknowledgement to Referees

Acknowledgement to Referees 2014

Research Article

A new family of choline kinase inhibitors with antiproliferative and antitumor activity derived from natural products

Research Article

Prognostic and predictive value of plasma D-dimer in advanced non-small cell lung cancer patients undergoing first-line chemotherapy
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits