Th22 cell accumulation is associated with colorectal cancer development

被引:50
作者
Huang, Yong-Hong [1 ]
Cao, Yun-Fei [1 ]
Jiang, Zhi-Yuan [1 ]
Zhang, Sen [1 ]
Gao, Feng [1 ]
机构
[1] Guangxi Med Univ, Dept Colorectal & Anal Surg, Affiliated Hosp 1, Nanning 530021, Guangxi Zhuang, Peoples R China
基金
中国国家自然科学基金;
关键词
Th22; cells; interleukin-22; STAT3; Colorectal cancer; Tumor microenvironment; INTERLEUKIN; 22; COLON-CANCER; T-CELLS; MOLECULAR PATHWAYS; SIGNALING PATHWAY; STAT3; EXPRESSION; IL-22; ACTIVATION; SURVIVAL;
D O I
10.3748/wjg.v21.i14.4216
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
AIM: To investigate the expression of Th22 cells and related cytokines in colorectal cancer (CRC) tissues, and the probably mechanism. METHODS: CRC tumor and paratumor tissues were collected to detect the expression levels of Th22 cells and of related cytokines by immunohistochemistry, flow cytometry and real-time quantitative polymerase chain reaction (RT-qPCR). interleukin (IL)-22 alone or with a STAT3 inhibitor was co-cultured with RKO cells in vitro to study the effects of IL-22 on colon cancer cells. IL-22 alone or with a STAT3 inhibitor was injected into a BALB/c nude mouse model with subcutaneously transplanted RKO cells to study the effects of IL-22 on colon cancer growth. RESULTS: The percentage of Th22 cells in the CD4(+) T subset was significantly higher in tumor tissues compared with that in paratumor tissues (1.47% +/- 0.083% vs 1.23% +/- 0.077%, P < 0.05) as determined by flow cytometry. RT-qPCR analysis revealed that the mRNA expression levels of IL-22, aryl hydrocarbon receptor, CCL20 and CCL22 were significantly higher in tumor tissues compared with those in paratumor tissues. CCL27 mRNA also displayed a higher expression level in tumor tissues compared with that in paratumor tissues; however, these levels were not significantly different (2.58 +/- 0.93 vs 2.30 +/- 0.78, P > 0.05). IL-22 enhanced colon cancer cell proliferation in vitro and displayed anti-apoptotic effects; these effects were blocked by adding a STAT3 inhibitor. IL-22 promoted tumor growth in BALB/c nude mice; however, this effect was reversed by adding a STAT3 inhibitor. CONCLUSION: Th22 cells that accumulate in CRC may be associated with the chemotactic effect of the tumor microenvironment. IL-22 is associated with CRC development, most likely via STAT3 activation.
引用
收藏
页码:4216 / 4224
页数:9
相关论文
共 33 条
[1]  
[Anonymous], 2020, CA Cancer J Clin, DOI DOI 10.3322/CAAC.21590
[2]   Epidemiological transition of colorectal cancer in developing countries: Environmental factors, molecular pathways, and opportunities for prevention [J].
Bishehsari, Faraz ;
Mahdavinia, Mahboobeh ;
Vacca, Michele ;
Malekzadeh, Reza ;
Mariani-Costantini, Renato .
WORLD JOURNAL OF GASTROENTEROLOGY, 2014, 20 (20) :6055-6072
[3]   Inflammation-related factors predicting prognosis of gastric cancer [J].
Chang, Wen-Jun ;
Du, Yan ;
Zhao, Xin ;
Ma, Li-Ye ;
Cao, Guang-Wen .
WORLD JOURNAL OF GASTROENTEROLOGY, 2014, 20 (16) :4586-4596
[4]   Molecular Pathways Involved in Colorectal Cancer: Implications for Disease Behavior and Prevention [J].
Colussi, Dora ;
Brandi, Giovanni ;
Bazzoli, Franco ;
Ricciardiello, Luigi .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2013, 14 (08) :16365-16385
[5]   Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells [J].
Duhen, Thomas ;
Geiger, Rebekka ;
Jarrossay, David ;
Lanzavecchia, Antonio ;
Sallusto, Federica .
NATURE IMMUNOLOGY, 2009, 10 (08) :857-U72
[6]   Annual Report to the Nation on the status of cancer, 1975-2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer [J].
Edwards, Brenda K. ;
Noone, Anne-Michelle ;
Mariotto, Angela B. ;
Simard, Edgar P. ;
Boscoe, Francis P. ;
Henley, S. Jane ;
Jemal, Ahmedin ;
Cho, Hyunsoon ;
Anderson, Robert N. ;
Kohler, Betsy A. ;
Eheman, Christie R. ;
Ward, Elizabeth M. .
CANCER, 2014, 120 (09) :1290-1314
[7]   Acute and Chronic Effects of IL-22 on Acetaminophen-Induced Liver Injury [J].
Feng, Dechun ;
Wang, Yan ;
Wang, Hua ;
Weng, Honglei ;
Kong, Xiaoni ;
Martin-Murphy, Brittany V. ;
Li, Yongmei ;
Park, Ogyi ;
Dooley, Steven ;
Ju, Cynthia ;
Gao, Bin .
JOURNAL OF IMMUNOLOGY, 2014, 193 (05) :2512-2518
[8]   IL-22 produced by cancer-associated fibroblasts promotes gastric cancer cell invasion via STAT3 and ERK signaling [J].
Fukui, H. ;
Zhang, X. ;
Sun, C. ;
Hara, K. ;
Kikuchi, S. ;
Yamasaki, T. ;
Kondo, T. ;
Tomita, T. ;
Oshima, T. ;
Watari, J. ;
Imura, J. ;
Fujimori, T. ;
Sasako, M. ;
Miwa, H. .
BRITISH JOURNAL OF CANCER, 2014, 111 (04) :763-771
[9]   Type, density, and location of immune cells within human colorectal tumors predict clinical outcome [J].
Galon, Jerom ;
Costes, Anne ;
Sanchez-Cabo, Fatima ;
Kirilovsky, Amos ;
Mlecnik, Bernhard ;
Lagorce-Pages, Christine ;
Tosolini, Marie ;
Camus, Matthieu ;
Berger, Anne ;
Wind, Philippe ;
Zinzindohoue, Franck ;
Bruneval, Patrick ;
Cugnenc, Paul-Henri ;
Trajanoski, Zlatko ;
Fridman, Wolf-Herman ;
Pages, Franck .
SCIENCE, 2006, 313 (5795) :1960-1964
[10]   Towards the introduction of the 'Immunoscore' in the classification of malignant tumours [J].
Galon, Jerome ;
Mlecnik, Bernhard ;
Bindea, Gabriela ;
Angell, Helen K. ;
Berger, Anne ;
Lagorce, Christine ;
Lugli, Alessandro ;
Zlobec, Inti ;
Hartmann, Arndt ;
Bifulco, Carlo ;
Nagtegaal, Iris D. ;
Palmqvist, Richard ;
Masucci, Giuseppe V. ;
Botti, Gerardo ;
Tatangelo, Fabiana ;
Delrio, Paolo ;
Maio, Michele ;
Laghi, Luigi ;
Grizzi, Fabio ;
Asslaber, Martin ;
D'Arrigo, Corrado ;
Vidal-Vanaclocha, Fernando ;
Zavadova, Eva ;
Chouchane, Lotfi ;
Ohashi, Pamela S. ;
Hafezi-Bakhtiari, Sara ;
Wouters, Bradly G. ;
Roehrl, Michael ;
Nguyen, Linh ;
Kawakami, Yutaka ;
Hazama, Shoichi ;
Okuno, Kiyotaka ;
Ogino, Shuji ;
Gibbs, Peter ;
Waring, Paul ;
Sato, Noriyuki ;
Torigoe, Toshihiko ;
Itoh, Kyogo ;
Patel, Prabhu S. ;
Shukla, Shilin N. ;
Wang, Yili ;
Kopetz, Scott ;
Sinicrope, Frank A. ;
Scripcariu, Viorel ;
Ascierto, Paolo A. ;
Marincola, Francesco M. ;
Fox, Bernard A. ;
Pages, Franck .
JOURNAL OF PATHOLOGY, 2014, 232 (02) :199-209