The stimulatory activity of plasma in patients with advanced non-small cell lung cancer requires TLR-stimulating nucleic acid immunoglobulin complexes and discriminates responsiveness to chemotherapy

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• 作者：Zengguang Xu (1) (2)
  Fengying Wu (3)
  Chunhong Wang (4)
  Xiyu Liu (5)
  Baoli Kang (2)
  Shan Shan (3)
  Xia Gu (4)
  Kailing Wang (4)
  Tao Ren (4)
  
  1. Department of Scientific Research ; East Hospital ; Tongji University School of Medicine ; Shanghai ; 200120 ; China
  2. Department of Preventive Medicine ; East Hospital ; Tongji University School of Medicine ; Shanghai ; China
  3. Department of Oncology ; Shanghai Pulmonary Hospital ; Tongji University School of Medicine ; Shanghai ; China
  4. Department of Respiratory Medicine ; East Hospital ; Tongji University School of Medicine ; 150 Jimo Road ; Pudong New Area ; Shanghai ; 200120 ; China
  5. Department of Chest Surgery ; The Bethune First Hospital of Jilin University ; Changchun ; China
  
• 关键词：Non ; small cell lung cancer ; Chemotherapy ; Toll ; like receptor ; Immune complex
• 刊名：Cancer Cell International
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：14
• 期：1
• 全文大小：1,489 KB
• 参考文献：1. Punnoose, EA, Atwal, S, Liu, W, Raja, R, Fine, BM, Hughes, BG, Hicks, RJ, Hampton, GM, Amler, LC, Pirzkall, A, Lackner, MR (2012) Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase II clinical trial of pertuzumab and erlotinib. Clin Cancer Res 18: pp. 2391-2401 new window">CrossRef
  2. Holdenrieder, S, Pawel, J, Dankelmann, E, Duell, T, Faderl, B, Markus, A, Siakavara, M, Wagner, H, Feldmann, K, Hoffmann, H, Raith, H, Nagel, D, Stieber, P (2009) Nucleosomes and CYFRA 21鈥? indicate tumor response after one cycle of chemotherapy in recurrent non-small cell lung cancer. Lung Cancer 63: pp. 128-135 new window">CrossRef
  3. Jemal, A, Siegel, R, Ward, E, Murray, T, Xu, J, Thun, MJ (2007) Cancer statistics, 2007. CA Cancer J Clin 57: pp. 43-66 new window">CrossRef
  4. Mountain, CF (2000) The international system for staging lung cancer. Semin Surg Oncol 18: pp. 106-115 new window">CrossRef
  5. Postel-Vinay, S, Vanhecke, E, Olaussen, KA, Lord, CJ, Ashworth, A, Soria, JC (2012) The potential of exploiting DNA-repair defects for optimizing lung cancer treatment. Nat Rev Clin Oncol 9: pp. 144-155 new window">CrossRef
  6. Lin, Y, Zhang, L, Cai, AX, Lee, M, Zhang, W, Neuberg, D, Canning, CM, Soiffer, RJ, Alyea, EP, Ritz, J, Hacohen, N, Means, TK, Wu, CJ (2011) Effective posttransplant antitumor immunity is associated with TLR-stimulating nucleic acid-immunoglobulin complexes in humans. J Clin Invest 121: pp. 1574-1584 new window">CrossRef
  7. Means, TK, Latz, E, Hayashi, F, Murali, MR, Golenbock, DT, Luster, AD (2005) Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J Clin Invest 115: pp. 407-417 new window">CrossRef
  8. Chiba, S, Baghdadi, M, Akiba, H, Yoshiyama, H, Kinoshita, I, Dosaka-Akita, H, Fujioka, Y, Ohba, Y, Gorman, JV, Colgan, JD, Hirashima, M, Uede, T, Takaoka, A, Yagita, H, Jinushi, M (2012) Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat Immunol 13: pp. 832-842 new window">CrossRef
  9. Enewold, L, Mechanic, LE, Bowman, ED, Zheng, YL, Yu, Z, Trivers, G, Alberg, AJ, Harris, CC (2009) Serum concentrations of cytokines and lung cancer survival in African Americans and Caucasians. Cancer Epidemiol Biomarkers Prev 18: pp. 215-222 new window">CrossRef
  10. Katsumata, N, Eguchi, K, Fukuda, M, Yamamoto, N, Ohe, Y, Oshita, F, Tamura, T, Shinkai, T, Saijo, N (1996) Serum levels of cytokines in patients with untreated primary lung cancer. Clin Cancer Res 2: pp. 553-559
  11. Tas, F, Duranyildiz, D, Argon, A, O臒uz, H, Camlica, H, Yasasever, V, Topuz, E (2005) Serum levels of leptin and proinflammatory cytokines in advanced-stage non-small cell lung cancer. Med Oncol 22: pp. 353-358 new window">CrossRef
  12. Song眉r, N, Kuru, B, Kalkan, F, Ozdilekcan, C, Cakmak, H, Hizel, N (2004) Serum interleukin-6 levels correlate with malnutrition and survival in patients with advanced non-small cell lung cancer. Tumori 90: pp. 196-200
  13. Akira, S, Uematsu, S, Takeuchi, O (2006) Pathogen recognition and innate immunity. Cell 124: pp. 783-801 new window">CrossRef
  14. Lee, CC, Avalos, AM, Ploegh, HL (2012) Accessory molecules for Toll-like receptors and their function. Nat Rev Immunol 12: pp. 168-179
  15. Kawai, T, Akira, S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11: pp. 373-384 new window">CrossRef
  16. O'Neill, LA, Golenbock, D, Bowie, AG (2013) The history of Toll-like receptors - redefining innate immunity. Nat Rev Immunol 13: pp. 453-460
  17. Kawai, T, Akira, S (2011) Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 34: pp. 637-650 new window">CrossRef
  18. Kutikhin, AG (2011) Association of polymorphisms in TLR genes and in genes of the Toll-like receptor signaling pathway with cancer risk. Hum Immunol 72: pp. 1095-1116 new window">CrossRef
  19. Hamm, S, Rath, S, Michel, S, Baumgartner, R (2009) Cancer immunotherapeutic potential of novel small molecule TLR7 and TLR8 agonists. J Immunotoxicol 6: pp. 257-265 new window">CrossRef
  20. Kaczanowska, S, Joseph, AM, Davila, E (2013) TLR agonists: our best frenemy in cancer immunotherapy. J Leukoc Biol 93: pp. 847-863 new window">CrossRef
  21. Pinto, A, Morello, S, Sorrentino, R (2011) Lung cancer and Toll-like receptors. Cancer Immunol Immunother 60: pp. 1211-1220 new window">CrossRef
  22. Manegold, C, Zandwijk, N, Szczesna, A, Zatloukal, P, Au, JS, Blasinska-Morawiec, M, Serwatowski, P, Krzakowski, M, Jassem, J, Tan, EH, Benner, RJ, Ingrosso, A, Meech, SJ, Readett, D, Thatcher, N (2012) A phase III randomized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung cancer. Ann Oncol 23: pp. 72-77 new window">CrossRef
  23. Yamada, K, Nakao, M, Fukuyama, C, Nokihara, H, Yamamoto, N, Sekine, I, Kunitoh, H, Ohe, Y, Ohki, E, Hashimoto, J, Tamura, T (2010) Phase I study of TLR9 agonist PF-3512676 in combination with carboplatin and paclitaxel in patients with advanced non-small-cell lung cancer. Cancer Sci 101: pp. 188-195 new window">CrossRef
  24. Ren, T, Wen, ZK, Liu, ZM, Qian, C, Liang, YJ, Jin, ML, Cai, YY, Xu, L (2008) Targeting toll-like receptor 9 with CpG oligodeoxynucleotides enhances anti-tumor responses of peripheral blood mononuclear cells from human lung cancer patients. Cancer Invest 26: pp. 448-455 new window">CrossRef
  25. Ren, T, Wen, ZK, Liu, ZM, Liang, YJ, Guo, ZL, Xu, L (2007) Functional expression of TLR9 is associated to the metastatic potential of human lung cancer cell: functional active role of TLR9 on tumor metastasis. Cancer Biol Ther 6: pp. 1704-1709 new window">CrossRef
  26. Xu, L, Zhou, Y, Liu, Q, Luo, JM, Qing, M, Tang, XY, Yao, XS, Wang, CH, Wen, ZK (2009) CXCR4/SDF-1 pathway is crucial for TLR9 agonist enhanced metastasis of human lung cancer cell. Biochem Biophys Res Commun 382: pp. 571-576 new window">CrossRef
  27. Ren, T, Xu, L, Jiao, S, Wang, Y, Cai, Y, Liang, Y, Zhou, Y, Zhou, H, Wen, Z (2009) TLR9 signaling promotes tumor progression of human lung cancer cell in vivo. Pathol Oncol Res 15: pp. 623-630 new window">CrossRef
  28. Xu, L, Wang, C, Wen, Z, Yao, X, Liu, Z, Li, Q, Wu, Z, Xu, Z, Liang, Y, Ren, T (2010) Selective up-regulation of CDK2 is critical for TLR9 signaling stimulated proliferation of human lung cancer cell. Immunol Lett 127: pp. 93-99 new window">CrossRef
  29. Wang, C, Fei, G, Liu, Z, Li, Q, Xu, Z, Ren, T (2012) HMGB1 was a pivotal synergistic effecor for CpG oligonucleotide to enhance the progression of human lung cancer cells. Cancer Biol Ther 13: pp. 727-736 new window">CrossRef
  30. Li, Q, Li, X, Guo, Z, Xu, F, Xia, J, Liu, Z, Ren, T (2012) MicroRNA-574-5p was pivotal for TLR9 signaling enhanced tumor progression via down-regulating checkpoint suppressor 1 in human lung cancer. PLoS One 7: pp. e48278 new window">CrossRef
  31. Xu, L, Wen, Z, Zhou, Y, Liu, Z, Li, Q, Fei, G, Luo, J, Ren, T (2013) MicroRNA-7-regulated TLR9 signaling-enhanced growth and metastatic potential of human lung cancer cells by altering the phosphoinositide-3-kinase, regulatory subunit 3/Akt pathway. Mol Biol Cell 24: pp. 42-55 new window">CrossRef
  32. Sorrentino, R, Morello, S, Giordano, MG, Arra, C, Maiolino, P, Adcock, IM, Pinto, A (2011) CpG-ODN increases the release of VEGF in a mouse model of lung carcinoma. Int J Cancer 128: pp. 2815-2822 new window">CrossRef
  33. Holdenrieder, S, Stieber, P, Pawel, J, Raith, H, Nagel, D, Feldmann, K, Seidel, D (2004) Circulating nucleosomes predict the response to chemotherapy in patients with advanced non-small cell lung cancer. Clin Cancer Res 10: pp. 5981-5987 new window">CrossRef
  
• 刊物主题：Cancer Research; Cell Biology;
• 出版者：BioMed Central
• ISSN：1475-2867

文摘

Background Therapeutic options for patients with non-small cell lung cancer (NSCLC) are often restricted to systemic chemotherapy. However, the molecular and cellular processes during chemotherapy of advanced NSCLC patients still remain unclear. Here we investigated the stimulatory activity of plasma in advanced NSCLC patients and its correlation with chemotherapy. Methods Whole blood samples from advanced NSCLC patients were collected before the first, second, and third cycle of chemotherapy. Plasma was isolated following centrifugation of whole blood. PBMCs were isolated from whole-blood specimens by Ficoll-Hypaque density gradient centrifugation. Immune complexes (ICs) were isolated from NSCLC plasma using the IgG Purification Kit. qRT-PCR was used to detect a broad array of cytokines and chemokines. Results The plasma in advanced NSCLC patients was endowed with stimulatory activity and capable of inducing proinflammatory cytokines. Both nucleic acids and immunoglobulin components were required for the stimulatory activity of NSCLC plasma. In consistent, TLR8 and TLR9 conferred the stimulatory activity of plasma in NSCLC patients. Of note, we revealed the decreased stimulatory activity of plasma in patients who responded to chemotherapy. Conclusions Our findings demonstrated that the plasma of advanced NSCLC patients required TLR-stimulating nucleic acid immunoglobulin complexes and could discriminate the responsiveness to chemotherapy, which might provide a novel mechanism by which the proinflammatory immune response was induced and a potential new biomarker for evaluating responsiveness to chemotherapy in NSCLC patients.