Efficacy of dendritic cells vaccines in colorectal cancer: a systematic review_Chinese Journal of Evidence-Based Medicine

Authors：

ZHANG Yating ¹ , CHEN Cong ^1,2 ,  LI Yumi ^2,3,4

1. The Second Clinical Medical College of Lanzhou University, Lanzhou, 730000, P.R.China;
2. Lanzhou University Second Hospital, Lanzhou, 730000, P.R.China;
3. Key Laboratory of Digestive System Tumors of Gansu Province, Lanzhou, 730000, P.R.China;
4. The Translational Medical Center for Biological Technology of Lanzhou University Second Hospital, Lanzhou, 730000, P.R.China;

Corresponding author：

LI Yumi, Email: liym@lzu.edu.cn

Keywords：

Colorectal cancer; Dendritic cell; Vaccine; Meta-analysis; Randomized controlled trial; Non-randomized controlled trial

DOI：

10.7507/1672-2531.201712035

Video：

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Objectives The aim of this meta-analysis was to evaluate the adjuvant efficacy of dendritic cell (DC) vaccines against advanced colorectal cancer.Methods CNKI, CBM, WanFang Data, VIP, PubMed, Web of Science, The Cochrane Library and EMbase were searched to identify studies on dendritic cell vaccine for CRC up to August 13^rd, 2017. After independently screening the literature and extracting data, two researchers evaluated the risk of bias in the studies, and used RevMan 5.3.5 software for meta-analysis.Results A total of 10 studies involving 2 050 patients were included. Meta-analysis showed that cellular immunotherapy based on DC vaccine treatment can improve the 2-year and 3-year overall survival rate of patients with advanced colorectal cancer (HR=0.33, 95%CI 0.17 to 0.27; 0.26, 95%CI 0.12 to 0.56, P<0.05), while there was no statistically significant difference in 1-year overall survival rate (HR=0.48, 95%CI 0.19 to 1.20, P=0.12); DC-CIK-based cellular immunotherapy could improve 2-year and 3-year overall survival rates (HR=0.27, 95%CI 0.10 to 0.75; HR=0.15, 95%CI 0.04 to 0.54, P<0.05), the difference of 1-year overall survival rate was not statistically significant (HR=0.39, 95%CI 0.13 to 1.13, P=0.08); DC combined with chemotherapy could improve 2-year and 3-year overall survival (HR=0.24, 95%CI 0.10 to 0.56; HR=0.22, 95%CI 0.04 to 0.54, P<0.05); the difference of 1-year overall survival rate was not statistically significant (HR=0.34, 95%CI 0.06 to 2.03, P=0.24); median overall survival in the DC vaccine group (MSR=1.25, 95%CI 1.16 to 1.34, P<0.05) and median progression-free survival (MSR=1.39, 95%CI 1.25 to 1.53, P<0.05) were superior to the control group. Fever was the most common adverse reaction and most patients could be relieved after treatment.Conclusions Dendritic cells vaccines-based immunotherapy can effectively improve the later overall survival rate and prolong median OS of patients with advanced colorectal cancer with mild adverse reactions, however the improvement of short term survival rate is not obvious.

Citation： ZHANG Yating, CHEN Cong, LI Yumi. Efficacy of dendritic cells vaccines in colorectal cancer: a systematic review. Chinese Journal of Evidence-Based Medicine, 2019, 19(3): 293-301. doi: 10.7507/1672-2531.201712035 Copy

1.	Li MX, Liu XM, Zhang XF, et al. Prognostic role of neutrophil to lymphocyte ratio in colorectal cancer: A systematic review and meta-analysis. Int J Cancer, 2014, 134(10): 2403-2413.
2.	Chau I, Cunningham D. Treatment in advanced colorectal cancer: what, when and how? Brit J Cancer, 2009, 100(11): 1704.
3.	柳海霞. 中国结直肠癌诊疗规范 (2015 版). 中华普通外科学文献 (电子版), 2015, 9(6): 506-523.
4.	Douillard JY, Cunningham D, Roth AD, et al. Colorectal cancer. Lancet, 2010, 375(9719): 1030-1047.
5.	Banchereau J, Palucka AK. Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol, 2005, 5(4): 296.
6.	Cheever MA, Higano CS. PROVENGE (Sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine. Clin Cancer Res, 2011, 17(11): 3520-3526.
7.	Devitar VT, Rosenberg SA. Two hundred years of cancer research. N Engl J Med, 2012, 366(23): 2207-2214.
8.	Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials, 1996, 17(1): 1-12.
9.	Slim K, Nini E, Forestier D, et al. Methodological index for nonrandomized studies (MINORS): development and validation of a new instrument. Anz J Surg, 2003, 73(9): 712-716.
10.	Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. J Stat Med, 2004, 23(11): 2815-2834.
11.	Altman DG, Bland M. Interaction revisited: the difference between two estimates. Brit Med J, 2003, 326(7382): 219.
12.	Lu D, Gu S, Du P, et al. Effect of immunotherapy on the immune function and survival of patients after colon cancer surgery. Int Clin Exp Med, 2016, 9(2): 1780-1786.
13.	Gao D, Li C, Xie X, et al. Autologous tumor lysate-pulsed dendritic cell immunotherapy with cytokine-induced killer cells improves survival in gastric and colorectal cancer patients. PLoS One, 2014, 9(4): e93886.
14.	Zhu H, Yang X, Li J, et al. Immune response, safety, and survival and quality of life outcomes for advanced colorectal cancer patients treated with dendritic cell vaccine and cytokine-induced killer cell therapy. Biomed Res Int, 2014, 2014: 603871.
15.	Lin T, Song C, Chuo D Y, et al. Clinical effects of autologous dendritic cells combined with cytokine-induced killer cells followed by chemotherapy in treating patients with advanced colorectal cancer: a prospective study. Tumor Biol, 2016, 37(4): 4367-4372.
16.	Maurel J, Caballerobanos M, Mila J, et al. Phase II randomised trial of autologous tumour lysate dendritic cell plus best supportive care compared with best supportive care in pre-treated advanced colorectal cancer patients. Eur J Cancer, 2016, 64: 167-174.
17.	Du XH, Liu HL, Li L, et al. Clinical significance of immunotherapy with combined three kinds of cells for operable colorectal cancer. Tumor Biol, 2015, 36(7): 5679-5685.
18.	Morse MA, Niedzwiecki D, Marshall JL, et al. A randomized phase II study of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer. Ann Surg, 2013, 258(6): 879-886.
19.	应敏刚, 魏植强, 杨建伟, 等. 结直肠癌术后放化疗联合 DC-CIK 的疗效分析. 实用癌症杂志, 2010, 25(3): 274-276.
20.	朱卫, 李佳丽, 张利红, 等. 自体免疫细胞治疗联合化疗治疗大肠癌的临床研究. 中国中西医结合外科杂志, 2016, 22(2): 116-119.
21.	魏植强, 杨建伟, 陈路川, 等. 直肠癌术后放化疗联合 DC-CIK 回顾性疗效分析. 福建医科大学学报, 2009, 43(6): 483-487.
22.	Chen W, Zheng R, Baade P D, et al. Cancer statistics in China, 2015. Ca-Cancer J Clin, 2016, 66(2): 115-132.
23.	Riedy M. Preventing colorectal cancer. Adv NPs Pas, 2013, 4(6): 18-21.
24.	De ICL, Henao CF, Vicente BD, et al. Immune microenvironment in colorectal cancer: a new hallmark to change old paradigms. Clin Dev Immuno, 2011, 2011: 174149.
25.	Rybojad P, Jabłonka A, Wilczyńska B, et al. Surgery decreases number of cells secreting cytotoxic mediators and increases secretion of interleukin 10 in patients with lung cancer. Eur J Surg Oncol, 2013, 39(11): 1269-1277.
26.	Feig C, Jones J O, Kraman M, et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti–PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci USA, 2013, 110(50): 20212-20217.
27.	Mace TA, Ameen Z, Collins A, et al. Pancreatic cancer-associated stellate cells promote differentiation of myeloid-derived suppressor cells in a STAT3-dependent manner. Cancer Res, 2013, 73(10): 3007-3018.
28.	Lambert LA, Gibson GR, Maloney M, et al. Intranodal immunization with tumor lysate-pulsed dendritic cells enhances protective antitumor immunity. Cancer Res, 2001, 61(2): 641-646.
29.	Irvine KR, Parkhurst MR, Shulman EP, et al. Recombinant virus vaccination against “self” antigens using anchor-fixed immunogens. Cancer Res, 1999, 59(11): 2536-2540.
30.	Toes RE, Ei VDV, Schoenberger SP, et al. Enhancement of tumor outgrowth through CTL tolerization after peptide vaccination is avoided by peptide presentation on dendritic cells. J Immunol, 1998, 160(9): 4449-4456.
31.	瞿霏霏, 黄伟谦, 张闯, 等. 树突状细胞疫苗联合射频消融术治疗结直肠癌肝转移临床疗效. 中国肿瘤生物治疗杂志, 2016, 23(1): 73-78.
32.	Günther K, Radkow T, Reymond M A, et al. Angiogenesis and dendritic cell density are not correlated with metachronous distant metastasis in curatively operated rectal cancer. Int J Colorectal Dis, 2003, 18(4): 300-308.
33.	Shapira S, Lisiansky V, Arber N, et al. Targeted immunotherapy for colorectal cancer: monoclonal antibodies and immunotoxins. Expert Opin Inv Drug, 2010, 19(Sup1): S67-S77.
34.	Dougan M, Dranoff G. Immune therapy for cancer. Annu Rev Immunol, 2009, 27(27): 83-117.
35.	Sangiolo D, Martinuzzi E, Todorovic M, et al. Alloreactivity and anti-tumor activity segregate within two distinct subsets of cytokine-induced killer (CIK) cells: implications for their infusion across major HLA barriers. Int Immunol, 2008, 20(7): 841-848.
36.	Zhang G, Zhao H, Wu J, et al. Adoptive immunotherapy for non-small cell lung cancer by NK and cytotoxic T lymphocytes mixed effector cells: retrospective clinical observation. Int Immunopharmacol, 2014, 21(2): 396-405.
37.	Introna M, Golay J, Rambaldi A. Cytokine Induced Killer (CIK) cells for the treatment of haematological neoplasms. Immunol Lett, 2013, 155(1): 27-30.
38.	Okada N. Cell delivery system: a novel strategy to improve the efficacy of cancer immunotherapy by manipulation of immune cell trafficking and biodistribution. Biol Pharm Bull, 2005, 28(9): 1543-1550.
39.	Lu PH, Negrin RS. A novel population of expanded human CD3+CD56+cells derived from T cells with potent in vivo antitumor activity in mice with severe combined immunodeficiency. J Immunol, 1994, 153(4): 1687-1696.
40.	Margolin KA, Negrin RS, Wong KK, et al. Cellular immunotherapy and autologous transplantation for hematologic malignancy. Immunol Rev, 1997, 157(1): 231-240.

1. Li MX, Liu XM, Zhang XF, et al. Prognostic role of neutrophil to lymphocyte ratio in colorectal cancer: A systematic review and meta-analysis. Int J Cancer, 2014, 134(10): 2403-2413.
2. Chau I, Cunningham D. Treatment in advanced colorectal cancer: what, when and how? Brit J Cancer, 2009, 100(11): 1704.
3. 柳海霞. 中国结直肠癌诊疗规范 (2015 版). 中华普通外科学文献 (电子版), 2015, 9(6): 506-523.
4. Douillard JY, Cunningham D, Roth AD, et al. Colorectal cancer. Lancet, 2010, 375(9719): 1030-1047.
5. Banchereau J, Palucka AK. Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol, 2005, 5(4): 296.
6. Cheever MA, Higano CS. PROVENGE (Sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine. Clin Cancer Res, 2011, 17(11): 3520-3526.
7. Devitar VT, Rosenberg SA. Two hundred years of cancer research. N Engl J Med, 2012, 366(23): 2207-2214.
8. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials, 1996, 17(1): 1-12.
9. Slim K, Nini E, Forestier D, et al. Methodological index for nonrandomized studies (MINORS): development and validation of a new instrument. Anz J Surg, 2003, 73(9): 712-716.
10. Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. J Stat Med, 2004, 23(11): 2815-2834.
11. Altman DG, Bland M. Interaction revisited: the difference between two estimates. Brit Med J, 2003, 326(7382): 219.
12. Lu D, Gu S, Du P, et al. Effect of immunotherapy on the immune function and survival of patients after colon cancer surgery. Int Clin Exp Med, 2016, 9(2): 1780-1786.
13. Gao D, Li C, Xie X, et al. Autologous tumor lysate-pulsed dendritic cell immunotherapy with cytokine-induced killer cells improves survival in gastric and colorectal cancer patients. PLoS One, 2014, 9(4): e93886.
14. Zhu H, Yang X, Li J, et al. Immune response, safety, and survival and quality of life outcomes for advanced colorectal cancer patients treated with dendritic cell vaccine and cytokine-induced killer cell therapy. Biomed Res Int, 2014, 2014: 603871.
15. Lin T, Song C, Chuo D Y, et al. Clinical effects of autologous dendritic cells combined with cytokine-induced killer cells followed by chemotherapy in treating patients with advanced colorectal cancer: a prospective study. Tumor Biol, 2016, 37(4): 4367-4372.
16. Maurel J, Caballerobanos M, Mila J, et al. Phase II randomised trial of autologous tumour lysate dendritic cell plus best supportive care compared with best supportive care in pre-treated advanced colorectal cancer patients. Eur J Cancer, 2016, 64: 167-174.
17. Du XH, Liu HL, Li L, et al. Clinical significance of immunotherapy with combined three kinds of cells for operable colorectal cancer. Tumor Biol, 2015, 36(7): 5679-5685.
18. Morse MA, Niedzwiecki D, Marshall JL, et al. A randomized phase II study of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer. Ann Surg, 2013, 258(6): 879-886.
19. 应敏刚, 魏植强, 杨建伟, 等. 结直肠癌术后放化疗联合 DC-CIK 的疗效分析. 实用癌症杂志, 2010, 25(3): 274-276.
20. 朱卫, 李佳丽, 张利红, 等. 自体免疫细胞治疗联合化疗治疗大肠癌的临床研究. 中国中西医结合外科杂志, 2016, 22(2): 116-119.
21. 魏植强, 杨建伟, 陈路川, 等. 直肠癌术后放化疗联合 DC-CIK 回顾性疗效分析. 福建医科大学学报, 2009, 43(6): 483-487.
22. Chen W, Zheng R, Baade P D, et al. Cancer statistics in China, 2015. Ca-Cancer J Clin, 2016, 66(2): 115-132.
23. Riedy M. Preventing colorectal cancer. Adv NPs Pas, 2013, 4(6): 18-21.
24. De ICL, Henao CF, Vicente BD, et al. Immune microenvironment in colorectal cancer: a new hallmark to change old paradigms. Clin Dev Immuno, 2011, 2011: 174149.
25. Rybojad P, Jabłonka A, Wilczyńska B, et al. Surgery decreases number of cells secreting cytotoxic mediators and increases secretion of interleukin 10 in patients with lung cancer. Eur J Surg Oncol, 2013, 39(11): 1269-1277.
26. Feig C, Jones J O, Kraman M, et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti–PD-L1 immunotherapy in pancreatic cancer. Proc Natl Acad Sci USA, 2013, 110(50): 20212-20217.
27. Mace TA, Ameen Z, Collins A, et al. Pancreatic cancer-associated stellate cells promote differentiation of myeloid-derived suppressor cells in a STAT3-dependent manner. Cancer Res, 2013, 73(10): 3007-3018.
28. Lambert LA, Gibson GR, Maloney M, et al. Intranodal immunization with tumor lysate-pulsed dendritic cells enhances protective antitumor immunity. Cancer Res, 2001, 61(2): 641-646.
29. Irvine KR, Parkhurst MR, Shulman EP, et al. Recombinant virus vaccination against “self” antigens using anchor-fixed immunogens. Cancer Res, 1999, 59(11): 2536-2540.
30. Toes RE, Ei VDV, Schoenberger SP, et al. Enhancement of tumor outgrowth through CTL tolerization after peptide vaccination is avoided by peptide presentation on dendritic cells. J Immunol, 1998, 160(9): 4449-4456.
31. 瞿霏霏, 黄伟谦, 张闯, 等. 树突状细胞疫苗联合射频消融术治疗结直肠癌肝转移临床疗效. 中国肿瘤生物治疗杂志, 2016, 23(1): 73-78.
32. Günther K, Radkow T, Reymond M A, et al. Angiogenesis and dendritic cell density are not correlated with metachronous distant metastasis in curatively operated rectal cancer. Int J Colorectal Dis, 2003, 18(4): 300-308.
33. Shapira S, Lisiansky V, Arber N, et al. Targeted immunotherapy for colorectal cancer: monoclonal antibodies and immunotoxins. Expert Opin Inv Drug, 2010, 19(Sup1): S67-S77.
34. Dougan M, Dranoff G. Immune therapy for cancer. Annu Rev Immunol, 2009, 27(27): 83-117.
35. Sangiolo D, Martinuzzi E, Todorovic M, et al. Alloreactivity and anti-tumor activity segregate within two distinct subsets of cytokine-induced killer (CIK) cells: implications for their infusion across major HLA barriers. Int Immunol, 2008, 20(7): 841-848.
36. Zhang G, Zhao H, Wu J, et al. Adoptive immunotherapy for non-small cell lung cancer by NK and cytotoxic T lymphocytes mixed effector cells: retrospective clinical observation. Int Immunopharmacol, 2014, 21(2): 396-405.
37. Introna M, Golay J, Rambaldi A. Cytokine Induced Killer (CIK) cells for the treatment of haematological neoplasms. Immunol Lett, 2013, 155(1): 27-30.
38. Okada N. Cell delivery system: a novel strategy to improve the efficacy of cancer immunotherapy by manipulation of immune cell trafficking and biodistribution. Biol Pharm Bull, 2005, 28(9): 1543-1550.
39. Lu PH, Negrin RS. A novel population of expanded human CD3+CD56+cells derived from T cells with potent in vivo antitumor activity in mice with severe combined immunodeficiency. J Immunol, 1994, 153(4): 1687-1696.
40. Margolin KA, Negrin RS, Wong KK, et al. Cellular immunotherapy and autologous transplantation for hematologic malignancy. Immunol Rev, 1997, 157(1): 231-240.

Chinese Journal of Evidence-Based Medicine

Efficacy of dendritic cells vaccines in colorectal cancer: a systematic review

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