CCR5 Blockade Suppresses Melanoma Development Through Inhibition of IL-6-Stat3 Pathway via Upregulation of SOCS3

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• 作者：Qiu Tang ; Jun Jiang ; Jian Liu
• 关键词：CCR5 ; IL ; 6 ; Stat3 ; SOCS3 ; melanoma
• 刊名：Inflammation
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：38
• 期：6
• 页码：2049-2056
• 全文大小：2,291 KB
• 参考文献：1.Stewart, T.J., and M.J. Smyth. 2009. Chemokine鈥攃hemokine receptors in cancer immunotherapy. Immunotherapy 1: 109鈥?27.CrossRef PubMed
  2.Murphy, P.M., M. Baggiolini, I.F. Charo, C.A. Hebert, R. Horuk, K. Matsushima, L.H. Miller, J.J. Oppenheim, and C.A. Power. 2000. International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacological Reviews 52: 145鈥?76.PubMed
  3.Luster, A.D. 1998. Chemokines鈥攃hemotactic cytokines that mediate inflammation. New England Journal of Medicine 338: 436鈥?45.CrossRef PubMed
  4.Schlecker, E., A. Stojanovic, C. Eisen, C. Quack, C.S. Falk, V. Umansky, and A. Cerwenka. 2012. Tumor-infiltrating monocytic myeloid-derived suppressor cells mediate CCR5-dependent recruitment of regulatory T cells favoring tumor growth. Journal of Immunology 189: 5602鈥?611.CrossRef
  5.Bedognetti, D., T.L. Spivey, Y. Zhao, L. Uccellini, S. Tomei, M.E. Dudley, M.L. Ascierto, V. De Giorgi, Q. Liu, L.G. Delogu, et al. 2013. CXCR3/CCR5 pathways in metastatic melanoma patients treated with adoptive therapy and interleukin-2. British Journal of Cancer 109: 2412鈥?423.PubMedCentral CrossRef PubMed
  6.Song, J.K., M.H. Park, D.Y. Choi, H.S. Yoo, S.B. Han, D.Y. Yoon, and J.T. Hong. 2012. Deficiency of C-C chemokine receptor 5 suppresses tumor development via inactivation of NF-kappaB and upregulation of IL-1Ra in melanoma model. PLoS One 7, e33747.PubMedCentral CrossRef PubMed
  7.Kim, H.K., H. Zhang, H. Li, T.T. Wu, S. Swisher, D. He, L. Wu, J. Xu, C.A. Elmets, M. Athar, X.C. Xu, and H. Xu. 2008. Slit2 inhibits growth and metastasis of fibrosarcoma and squamous cell carcinoma. Neoplasia 10: 1411鈥?420.PubMedCentral CrossRef PubMed
  8.Katz, A., L.M. Shulman, M. Revel, M. Feldman, and L. Eisenbach. 1993. Combined therapy with IL-6 and inactivated tumor cells suppresses metastasis in mice bearing 3LL lung carcinomas. International Journal of Cancer Journal International du Cancer 53: 812鈥?18.CrossRef PubMed
  9.Horiguchi, A., T. Asano, K. Kuroda, A. Sato, J. Asakuma, K. Ito, et al. 2010. STAT3 inhibitor WP1066 as a novel therapeutic agent for renal cell carcinoma. British Journal of Cancer 102: 1592鈥?599.PubMedCentral CrossRef PubMed
  10.Gabrilovich, D.I., and S. Nagaraj. 2009. Myeloid-derived suppressor cells as regulators of the immune system. Nature Reviews Immunology 9: 162鈥?74.PubMedCentral CrossRef PubMed
  11.Marigo, I., L. Dolcetti, P. Serafini, P. Zanovello, and V. Bronte. 2008. Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells. Immunological Reviews 222: 162鈥?79.CrossRef PubMed
  12.Bronte, V., and P. Zanovello. 2005. Regulation of immune responses by L-arginine metabolism. Nature Reviews Immunology 5: 641鈥?54.CrossRef PubMed
  13.Karin, M., Y. Cao, F.R. Greten, and Z.W. Li. 2002. NF-kappaB in cancer: from innocent bystander to major culprit. Nature Reviews Cancer 2: 301鈥?10.CrossRef PubMed
  14.Lee, N.J., D.Y. Choi, J.K. Song, Y.Y. Jung, D.H. Kim, T.M. Kim, D.J. Kim, S.M. Kwon, K.B. Kim, K.E. Choi, et al. 2012. Deficiency of C-C chemokine receptor 5 suppresses tumor development via inactivation of NF-kappaB and inhibition of monocyte chemoattractant protein-1 in urethane-induced lung tumor model. Carcinogenesis 33: 2520鈥?528.CrossRef PubMed
  15.Yu, H., M. Kortylewski, and D. Pardoll. 2007. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nature Reviews Immunology 7: 41鈥?1.CrossRef PubMed
  16.Hirano, T., K. Ishihara, and M. Hibi. 2000. Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene 19: 2548鈥?556.CrossRef PubMed
  17.Wormald, S., and D.J. Hilton. 2004. Inhibitors of cytokine signal transduction. Journal of Biological Chemistry 279: 821鈥?24.CrossRef PubMed
  18.Pandey, M.K., B. Sung, and B.B. Aggarwal. 2010. Betulinic acid suppresses STAT3 activation pathway through induction of protein tyrosine phosphatase SHP-1 in human multiple myeloma cells. International Journal of Cancer 127: 282鈥?92.
  19.Ostrand-Rosenberg, S., and P. Sinha. 2009. Myeloid-derived suppressor cells: linking inflammation and cancer. Journal of Immunology 182: 4499鈥?506.CrossRef
  20.Chandra, D., and C. Gravekamp. 2013. Myeloid-derived suppressor cells: cellular missiles to target tumors. Oncoimmunology 2, e26967.PubMedCentral CrossRef PubMed
  21.Liu, C., S. Yu, J. Kappes, J. Wang, W.E. Grizzle, K.R. Zinn, and H.G. Zhang. 2007. Expansion of spleen myeloid suppressor cells represses NK cell cytotoxicity in tumor-bearing host. Blood 109: 4336鈥?342.PubMedCentral CrossRef PubMed
  22.Darnell Jr., J.E. 1997. STATs and gene regulation. Science 277: 1630鈥?635.CrossRef PubMed
  23.Jarnicki, A., T. Putoczki, and M. Ernst. 2010. Stat3: linking inflammation to epithelial cancer鈥攎ore than a 鈥済ut鈥?feeling? Cell Division 5: 14.PubMedCentral CrossRef PubMed
  24.Aoki, Y., G.M. Feldman, and G. Tosato. 2003. Inhibition of STAT3 signaling induces apoptosis and decreases survivin expression in primary effusion lymphoma. Blood 101: 1535鈥?542.CrossRef PubMed
  25.Yu, H., and R. Jove. 2004. The STATs of cancer鈥攏ew molecular targets come of age. Nature Reviews Cancer 4: 97鈥?05.CrossRef PubMed
  26.Endo, T.A., M. Masuhara, M. Yokouchi, R. Suzuki, H. Sakamoto, K. Mitsui, A. Matsumoto, S. Tanimura, M. Ohtsubo, H. Misawa, et al. 1997. A new protein containing an SH2 domain that inhibits JAK kinases. Nature 387: 921鈥?24.CrossRef PubMed
  27.Yoshimura, A., T. Naka, and M. Kubo. 2007. SOCS proteins, cytokine signalling and immune regulation. Nature Reviews Immunology 7: 454鈥?65.CrossRef PubMed
  
• 作者单位：Qiu Tang (1)
  Jun Jiang (1)
  Jian Liu (2)
  
  1. Department of Oncology, Central Hospital of Wuhan, Wuhan Shengli Road 26#, Wuhan, Hubei, China
  2. Department of Oncology, People鈥檚 Liberation Army, Wuhan General Hospital of Guangzhou Command, Wuhan, Hubei, China
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Rheumatology
  Internal Medicine
  Pharmacology and Toxicology
  Pathology
  
• 出版者：Springer Netherlands
• ISSN：1573-2576

文摘

In order to understand how tumor cells can escape immune surveillance mechanisms and thus develop antitumor therapies, it is critically important to investigate the mechanisms by which the immune system interacts with the tumor microenvironment. In our current study, we found that chemokine receptor 5 (CCR5) neutralization resulted in reduced melanoma tumor size, decreased percentage of CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs), and increased proportion of cluster of differentiation (CD)3+ T cells in tumor tissues. Suppressive activity of MDSCs on CD4+ T cells and CD8+ T cell proliferation is significantly inhibited by anti-CCR5 antibody. CCR5 blockade also suppresses interleukin (IL)-6 induction, which in turn deactivates signal transducer and activator of transcription 3 (Stat3) in tumors. Furthermore, the suppressed B16 tumor growth induced by CCR5 blockade is abolished with additional administration of recombinant IL-6. CCR5 blockade also induces suppressor of cytokine signaling 3 (SOCS3) upregulations, and anti-CCR5 antibody fails to suppress expression of phospho-Stat3 (p-Stat3), matrix metallopeptidase 9 (MMP9), and IL-6 in cells transfected with SOCS3 short-interfering RNA (SiRNA). All these data suggest that CCR5 blockade suppresses melanoma development through inhibition of IL-6-Stat3 pathway via upregulation of SOCS3. KEY WORDS CCR5 IL-6 Stat3 SOCS3 melanoma