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 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 2/2017

Open Access 01-02-2017 | Original Article

Elevated systemic interleukin-7 in patients with colorectal cancer and individuals at high risk of cancer: association with lymph node involvement and tumor location in the right colon

Authors: Malgorzata Krzystek-Korpacka, Marek Zawadzki, Katarzyna Neubauer, Iwona Bednarz-Misa, Sabina Górska, Jerzy Wiśniewski, Wojciech Witkiewicz, Andrzej Gamian

Published in: Cancer Immunology, Immunotherapy | Issue 2/2017

Login to get access

Abstract

Interleukin (IL)-7 is a cytokine essential for protective immunity, and it is considered as a promising agent for cancer immunotherapy. Recent studies, however, appear to associate IL-7 with aggressiveness of solid tumors. The IL-7 has been less studied in colorectal cancer (CRC) and conditions associated with increased risk of CRC development. To explore IL-7 status in bowel diseases, it was measured immunofluorometrically in 431 individuals (110 with CRC) by using Luminex platform. A level of IL-7 in CRC patients was significantly higher than in controls, did not differ from those with adenomas, but was lower than in both active and inactive inflammatory bowel disease (IBD) cases. In CRC, IL-7 was higher in patients with lymph node and distant metastases and with tumors located in right colon. In adenomas, IL-7 elevation was associated exclusively with villous growth pattern, while in IBD, circulating IL-7 reflected clinical activity of Crohn’s disease and ulcerative colitis. Systemic TNFα, IL-10, and PDGF-BB were independent predictors of circulating IL-7. In summary, our study is the first to demonstrate IL-7 elevation in CRC in association with metastatic disease and tumor location. Both associations should be considered when designing IL-7-based immunotherapies for CRC. Further studies on IL-7 functionality in CRC are necessary.
Literature
1.
Siegel RL, Sahar L, Portier KM, Ward EM, Jemal A (2015) Cancer death rates in US congressional districts. CA Cancer J Clin 65:339–344CrossRefPubMed
2.
Chen W, Zheng R, Zeng H, Zhang S (2015) The updated incidences and mortalities of major cancers in China, 2011. Chin J Cancer 34:502–507PubMed
3.
Armaghany T, Wilson JD, Chu Q, Mills G (2012) Genetic alterations in colorectal cancer. Gastrointest Cancer Res 5:19–27PubMedPubMedCentral
4.
Yamaji Y, Mitsushima T, Ikuma H, Watabe H, Okamoto M, Kawabe T et al (2004) Incidence and recurrence rates of colorectal adenomas estimated by annually repeated colonoscopies on asymptomatic Japanese. Gut 53:568–572CrossRefPubMedPubMedCentral
5.
Fleming M, Ravula S, Tatishchev SF, Wang HL (2012) Colorectal carcinoma: pathologic aspects. J Gastrointest Oncol 3:153–173PubMedPubMedCentral
6.
7.
8.
9.
10.
Sportès C, Babb RR, Krumlauf MC, Hakim FT, Steinberg SM, Chow CK et al (2010) Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy. Clin Cancer Res 16:727–735CrossRefPubMedPubMedCentral
11.
Gao J, Zhao L, Wan YY, Zhu B (2015) Mechanism of action of IL-7 and its potential applications and limitations in cancer immunotherapy. Int J Mol Sci 16:10267–10280CrossRefPubMedPubMedCentral
12.
Perna SK, Pagliara D, Mahendravada A, Liu H, Brenner MK, Savoldo B et al (2014) Interleukin-7 mediates selective expansion of tumor-redirected cytotoxic T lymphocytes without enhancement of regulatory Tcell inhibition. Clin Cancer Res 20:131–139CrossRefPubMed
13.
Rosenberg SA, Sportès C, Ahmadzadeh M, Fry TJ, Ngo LT, Schwarz SL et al (2006) IL-7 administration to humans leads to expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells. J Immunother 29:313–319CrossRefPubMedPubMedCentral
14.
15.
16.
Maeurer MJ, Walter W, Martin D, Zitvogel L, Elder E, Storkus W et al (1997) Interleukin-7 (IL-7) in colorectal cancer: IL-7 is produced by tissues from colorectal cancer and promotes preferential expansion of tumour infiltrating lymphocytes. Scand J Immunol 45:182–192CrossRefPubMed
17.
Al-Rawi MA, Mansel RE, Jiang WG (2003) Interleukin-7 (IL-7) and IL-7 receptor (IL-7R) signalling complex in human solid tumours. Histol Histopathol 18:911–923PubMed
18.
Mengus C, Le Magnen C, Trella E, Yousef K, Bubendorf L, Provenzano M et al (2011) Elevated levels of circulating IL-7 and IL-15 in patients with early stage prostate cancer. J Transl Med 9:162CrossRefPubMedPubMedCentral
19.
Roato I, Caldo D, Godio L, D’Amico L, Giannoni P, Morello E et al (2010) Bone invading NSCLC cells produce IL-7: mice model and human histologic data. BMC Cancer 10:12CrossRefPubMedPubMedCentral
20.
Berghella AM, Contasta I, Pellegrini P, Del Beato T, Adorno D (2002) Peripheral blood immunological parameters for use as markers of pre-invasive to invasive colorectal cancer. Cancer Biother Radiopharm 17:43–50CrossRefPubMed
21.
Crucitti A, Corbi M, Tomaiuolo PM, Fanali C, Mazzari A, Lucchetti D et al (2015) Laparoscopic surgery for colorectal cancer is not associated with an increase in the circulating levels of several inflammation-related factors. Cancer Biol Ther 16:671–677CrossRefPubMedPubMedCentral
22.
Komura T, Sakai Y, Harada K, Kawaguchi K, Takabatake H, Kitagawa H et al (2015) Inflammatory features of pancreatic cancer highlighted by monocytes/macrophages and CD4+ T cells with clinical impact. Cancer Sci 106:672–686CrossRefPubMedPubMedCentral
23.
Provatopoulou X, Georgiadou D, Sergentanis TN, Kalogera E, Spyridakis J, Gounaris A et al (2014) Interleukins as markers of inflammation in malignant and benign thyroid disease. Inflamm Res 63:667–674CrossRefPubMed
24.
Chen ZY, He WZ, Peng LX, Jia WH, Guo RP, Xia LP et al (2015) A prognostic classifier consisting of 17 circulating cytokines is a novel predictor of overall survival for metastatic colorectal cancer patients. Int J Cancer 136:584–592PubMed
25.
Zhang W, Du JY, Yu Q, Jin JO (2015) Interleukin-7 produced by intestinal epithelial cells in response to Citrobacter rodentium infection plays a major role in innate immunity against this pathogen. Infect Immun 83:3213–3223CrossRefPubMedPubMedCentral
26.
Ujiie H, Kadota K, Nitadori JI, Aerts JG, Woo KM, Sima CS et al (2015) The tumoral and stromal immune microenvironment in malignant pleural mesothelioma: a comprehensive analysis reveals prognostic immune markers. Oncoimmunology 4:e1009285CrossRefPubMedPubMedCentral
27.
Henry CJ, Sedjo RL, Rozhok A, Salstrom J, Ahnen D, Levin TR et al (2015) Lack of significant association between serum inflammatory cytokine profiles and the presence of colorectal adenoma. BMC Cancer 15:123CrossRefPubMedPubMedCentral
28.
Comstock SS, Xu D, Hortos K, Kovan B, McCaskey S, Pathak DR et al (2016) Association of serum cytokines with colorectal polyp number and type in adult males. Eur J Cancer Prev 25:173–181CrossRefPubMed
29.
Kim S, Keku TO, Martin C, Galanko J, Woosley JT, Schroeder JC et al (2008) Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res 68:323–328CrossRefPubMedPubMedCentral
30.
Krzystek-Korpacka M, Diakowska D, Kapturkiewicz B, Bebenek M, Gamian A (2013) Profiles of circulating inflammatory cytokines in colorectal cancer (CRC), high cancer risk conditions, and health are distinct. Possible implications for CRC screening and surveillance. Cancer Lett 337:107–114CrossRefPubMed
31.
Krzystek-Korpacka M, Diakowska D, Neubauer K, Gamian A (2013) Circulating midkine in malignant and non-malignant colorectal diseases. Cytokine 64:158–164CrossRefPubMed
32.
Mattar MC, Lough D, Pishvaian MJ, Charabaty A (2011) Current management of inflammatory bowel disease and colorectal cancer. Gastrointest Cancer Res 4:53–61PubMedPubMedCentral
33.
Watanabe M, Watanabe N, Iwao Y, Ogata H, Kanai T, Ueno Y et al (1997) The serum factor from patients with ulcerative colitis that induces T-cell proliferation in the mouse thymus is interleukin-7. J Clin Immunol 17:282–292CrossRefPubMed
34.
Kader HA, Tchernev VT, Satyaraj E, Lejnine S, Kotler G, Kingsmore SF et al (2005) Protein microarray analysis of disease activity in pediatric inflammatory bowel disease demonstrates elevated serum PLGF, IL-7, TGF-beta1, and IL-12p40 levels in Crohn’s disease and ulcerative colitis patients in remission versus active disease. Am J Gastroenterol 100:414–423CrossRefPubMedPubMedCentral
35.
Korolkova OY, Myers JN, Pellom ST, Wang L, M’Koma AE (2015) Characterization of serum cytokine profile in predominantly colonic inflammatory bowel disease to delineate ulcerative and Crohn’s colitides. Clin Med Insights Gastroenterol 8:29–44PubMedPubMedCentral
36.
Funderburg NT, Stubble Park SR, Sung HC, Hardy G, Clagett B, Ignatz-Hoover J et al (2013) Circulating CD4+ and CD8+T-cells are activated in inflammatory bowel disease and are associated with plasma markers of inflammation. Immunology 140:87–97CrossRefPubMedPubMedCentral
37.
Lee JC, Lyons PA, McKinney EF, Sowerby JM, Carr EJ, Bredin F et al (2011) Gene expression profiling of CD8+ T-cells predicts prognosis in patients with Crohn disease and ulcerative colitis. J Clin Investig 121:4170–4179CrossRefPubMedPubMedCentral
38.
Shive CL, Mudd JC, Funderburg NT, Sieg SF, Kyi B, Bazdar DA et al (2014) Inflammatory cytokines drive CD4+ T-cell cycling and impaired responsiveness to interleukin 7: implications for immune failure in HIV disease. J Infect Dis 210:619–629CrossRefPubMedPubMedCentral
39.
Ming J, Zhang QF, Jiang YD, Jiang GC, Qiu XS (2015) Anti-lymphangiogenesis effects of a specific antiinterleukin 7 receptor antibody in lung cancer model in vivo. Mol Carcinog 54:148–155CrossRef
40.
Al-Rawi MA, Rmali K, Watkins G, Mansel RE, Jiang WG (2004) Aberrant expression of interleukin-7 (IL-7) and its signaling complex in human breast cancer. Eur J Cancer 40:494–502CrossRefPubMed
41.
Kadota K, Yeh YC, Villena-Vargas J, Cherkassky L, Drill EN, Sima CS et al (2015) Tumor budding correlates with the protumor immune microenvironment and is an independent prognostic factor for recurrence of stage I lung adenocarcinoma. Chest 148:711–721CrossRefPubMedPubMedCentral
42.
Liu ZH, Wang MH, Ren HJ, Qu W, Sun LM, Zhang QF et al (2014) Interleukin 7 signaling prevents apoptosis by regulating bcl-2 and bax via the p53 pathway in human non-small cell lung cancer cells. Int J Clin Exp Pathol 7:870–881PubMedPubMedCentral
43.
44.
Glebov OK, Rodriguez LM, Nakahara K, Jenkins J, Cliatt J, Humbyrd CJ et al (2003) Distinguishing right from left colon by the pattern of gene expression. Cancer Epidemiol Biomarkers Prev 12:755–762PubMed
45.
Derwinger K, Gustawsson B (2011) Variations in demography and prognosis by colon cancer location. Anticancer Res 31:2347–2350PubMed
46.
Yoshioka A, Okamoto R, Oshima S, Akiyama J, Tsuchiya K, Nakamura T et al (2008) Flagellin stimulation suppresses IL-7 secretion of intestinal epithelial cells. Cytokine 44:57–64CrossRefPubMed
47.
Ramello MC, Boari JT, Canale FP, Mena HA, Negrotto S, Gastman B et al (2014) Tumor-induced senescent T cells promote the secretion of pro-inflammatory cytokines and angiogenic factors by human monocytes/macrophages through a mechanism that involves Tim-3 and CD40L. Cell Death Dis 5:e1507CrossRefPubMedPubMedCentral
48.
Wu D, Wu P, Wu X, Ye J, Wang Z, Zhao S et al (2015) Ex vivo expanded human circulating Vδ1 γδT cells exhibit favorable therapeutic potential for colon cancer. Oncoimmunology 4:e992749CrossRefPubMedPubMedCentral
49.
Zhao L, Mei Y, Sun Q, Guo L, Wu Y, Yu X et al (2014) Autologous tumor vaccine modified with recombinant new castle disease virus expressing IL-7 promotes antitumor immune response. J Immunol 193:735–745CrossRefPubMed
50.
Evans C, Dalgleish AG, Kumar D (2006) Immune suppression and colorectal cancer. Aliment Pharmacol Ther 24:1163–1177CrossRefPubMed
Metadata
Title
Elevated systemic interleukin-7 in patients with colorectal cancer and individuals at high risk of cancer: association with lymph node involvement and tumor location in the right colon
Authors
Malgorzata Krzystek-Korpacka
Marek Zawadzki
Katarzyna Neubauer
Iwona Bednarz-Misa
Sabina Górska
Jerzy Wiśniewski
Wojciech Witkiewicz
Andrzej Gamian
Publication date
01-02-2017
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 2/2017
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-016-1933-3

Other articles of this Issue 2/2017

Cancer Immunology, Immunotherapy 2/2017 Go to the issue

Focussed Research Review

Rejection versus escape: the tumor MHC dilemma

Original Article

Immunogenicity and efficacy of a rationally designed vaccine against vascular endothelial growth factor in mouse solid tumor models

Focussed Research Review

Immunosenescence: limitations of natural killer cell-based cancer immunotherapy

Original Article

Oncolysate-loaded Escherichia coli bacterial ghosts enhance the stimulatory capacity of human dendritic cells

Focussed Research Review

Using natural products to promote caspase-8-dependent cancer cell death

Meeting Report

The fifteenth International Conference on Progress in Vaccination against Cancer (PIVAC-15), 6–8 October 2015, Tübingen, Germany: looking back on 15 years of progress
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