JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2015, Vol. 53 ›› Issue (7): 19-23.doi: 10.6040/j.issn.1671-7554.0.2014.977

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Antitumor effect of endostatin synergized with tumor special DC-T cellular therapy

LI Xingyu, LIANG Jing, LI Yan   

  1. Department of Chemotherapy, Cancer Center, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong, China
  • Received:2014-12-21 Revised:2015-04-28 Online:2015-07-10 Published:2015-07-10

Abstract: Objective To investigate the antitumor effect of endostatin combined with tumor special DC-T cellular therapy on lung cancer in Lewis mice. Methods C57BL/6 mice models were established. Tumor antigen special DC-T cells from spleen cells and mice bones were cultured in vitro. The tumor-bearing mice were randomly divided into three groups: A group (PBS control group), B group (DC-T group), and C group (DC-T+endostatin group). The body weight of mice and tumor volume were measured. The VEGF and HIF-1α expressions were determined with Western blotting. The proportions of MDSC, TAM (M1/M2), mDC and CD8+T in suspended tumor cells of tumor tissues were detected with FCM. Results Compared with that in A group, tumor growth in B group (P<0.05) and C group (P<0.01) were inhibited; VEGF expression decreased while HIF-1α expression increased in B group (P<0.05) and C group (P<0.01); the proportions of MDSC and TAM (M2 type) were reduced, while proportions of mDC, TAM (M1 type) and CD8+T cells were elevated in B group (P<0.05) and C group (P<0.01). Conclusion Tumor special DC-T cells combined with endostatin strongly reduce tumor growth, and efficiently reverse the immunosuppression of tumor microenvironment, exhibiting synergistic and much better antitumor effects than monotherapy strategy.

Key words: Cellular therapy, Angiogenesis, Lung neoplasm, Endostatin, Tumor microenvironment

CLC Number: 

  • R73-36+2
[1] Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012[J]. CA Cancer J Clin, 2012, 62(1): 10-29.
[2] Sharma P, Wagner K, Wolchok JD, et al. Novel cancer immunotherapy agents with survival benefit: recent successes and next steps[J]. Nat Rev Cancer, 2011, 11(11): 805-812.
[3] Rosenberg SA. Overcoming obstacles to the effective immunotherapy of human cancer[J]. Proc Natl Acad Sci U S A, 2008, 105(35): 12643-12644.
[4] Keibel A, Singh V, Sharma MC. Inflammation, microenvironment, and the immune system in cancer progression[J]. Curr Pharm Des, 2009, 15(17): 1949-1955.
[5] Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer[J]. Cell, 2010, 140(6): 883-899.
[6] Vasievich EA, Huang L. The suppressive tumor microenvironment: a challenge in cancer immunotherapy[J]. Mol Pharm, 2011, 8(3): 635-641.
[7] Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation[J]. Cell, 2011, 144(5): 646-674.
[8] Sonpavde G, Agarwal N, Choueiri TK, et al. Recent advances in immunotherapy for the treatment of prostate cancer[J]. Expert Opin Biol Ther, 2011, 11(8): 997-1009.
[9] Ko JS, Zea AH, Rini BI, et al. Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients[J]. Clin Cancer Res, 2009, 15(6): 2148-2157.
[10] Ozao-Choy J, Ma G, Kao J, et al. The novel role of tyrosine kinase inhibitor in the reversal of immune suppression and modulation of tumor microenvironment for immune-based cancer therapies[J]. Cancer Res, 2009, 69(6): 2514-2522.
[11] Rosenberg SA. Cell transfer immunotherapy for metastatic solid cancer-what clinicians need to know[J]. Nat Rev Clin Oncol, 2011, 8(10): 577-585.
[12] Griffioen AW. Anti-angiogenesis: making the tumor vulnerable to the immune system[J]. Cancer Immunol Immunother, 2008, 57(10): 1553-1558.
[13] De Bock K, Mazzone M, Carmeliet P. Antiangiogenic therapy, hypoxia, and metastasis: risky liaisons, or not?[J]. Nat Rev Clin Oncol, 2011, 8(7):393-404.
[14] Teicher BA. Antiangiogenic agents and targets: a perspective[J]. Biochem Pharmacol, 2011, 81(1): 6-12.
[15] Schoenfeld J, Jinushi M, Nakazaki Y, et al. Active immunotherapy induces antibody responses that target tumor angiogenesis[J]. Cancer Res, 2010, 70(24): 10150-10160.
[16] Nair S, Boczkowski D, Moeller B, et al. Synergy between tumor immunotherapy and antiangiogenic therapy[J]. Blood, 2003, 102(3): 964 -971.
[17] Ebos JM, Kerbel RS. Antiangiogenic therapy: impact on invasion, disease progression, and metastasis[J]. Nat Rev Clin Oncol, 2011, 8(4): 210-221.
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