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Clinical significance of immunotherapy with combined three kinds of cells for operable colorectal cancer

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Tumor Biology

Abstract

Surgery, chemotherapy, and radiotherapy have presented with the ability of killing tumor cells, as well as damaging the immune function, which can be corrected by the immunotherapy. The purpose of this perspective cohort study was to evaluate the efficacy of postoperative immunotherapies of tumor lysate-loaded dendritic cells (DC), in vitro DC-activated T (DC-AT), and activated T cells (ATC) combined with chemotherapy on the survival of patients with operable colorectal cancer. A total of 253 patients with primary colorectal cancer resection including 181patients receiving postoperative simple chemotherapy (control group) and 72 patients receiving immunotherapies of DC, DC-AT, and ATC combined with chemotherapy during the corresponding period (immunotherapy group) were enrolled in this perspective cohort study. The survival of these patients was analyzed. The immunotherapy group presented a higher 5-year overall survival rate than the control group (75.63 vs 67.81 %, P = 0.035), as well as 3-year overall survival rate (87.07 vs 74.80 %, P = 0.045). For patients with advanced cancer (TNM stages III and IV), immunotherapy significantly promotes mean survival than control subjects (59.74 ± 3.21 vs 49.99 ± 2.54 years, P = 0.034). Patients who received more than three cycles of immunotherapies had a higher 5-year overall survival rate than those with less than three cycles (82.10 vs 69.90 %, P = 0.035). No serious adverse effect was observed in the immunotherapy group. Postoperative immunotherapies with DC, DC-AT, and ATC combination can promote the survival of patients with operable colorectal cancer (Clinical Trials, ChiCTR-OCH-12002610).

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References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.

    Article  PubMed  Google Scholar 

  2. Fang YJ, Wu XJ, Zhao Q, Li LR, Lu ZH, Ding PR, et al. Hospital-based colorectal cancer survival trend of different tumor locations from 1960s to 2000s. PLoS ONE. 2013;8:e73528.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. DeVita Jr VT, Rosenberg SA. Two hundred years of cancer research. N Engl J Med. 2012;366:2207–14.

    Article  CAS  PubMed  Google Scholar 

  4. Cheever MA, Higano CS. Provenge (sipuleucel-t) in prostate cancer: the first FDA-approved therapeutic cancer vaccine. Clin Cancer Res Off J Am Assoc Cancer Res. 2011;17:3520–6.

    Article  Google Scholar 

  5. Zhao H, Fan Y, Li H, Yu J, Liu L, Cao S, Ren B, Yan F, Ren X. Immunotherapy with cytokine-induced killer cells as an adjuvant treatment for advanced gastric carcinoma: a retrospective study of 165 patients. Cancer Biother Radiopharm. 2013.

  6. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411–22.

    Article  CAS  PubMed  Google Scholar 

  7. Tamir A, Basagila E, Kagahzian A, Jiao L, Jensen S, Nicholls J, et al. Induction of tumor-specific T-cell responses by vaccination with tumor lysate-loaded dendritic cells in colorectal cancer patients with carcinoembryonic-antigen positive tumors. Cancer Immunol Immunother CII. 2007;56:2003–16.

    Article  PubMed  Google Scholar 

  8. Mann DL, Celluzzi CM, Hankey KG, Harris KM, Watanabe R, Hasumi K. Combining conventional therapies with intratumoral injection of autologous dendritic cells and activated T cells to treat patients with advanced cancers. Ann N Y Acad Sci. 2009;1174:41–50.

    Article  CAS  PubMed  Google Scholar 

  9. Thanendrarajan S, Nowak M, Abken H, Schmidt-Wolf IG. Combining cytokine-induced killer cells with vaccination in cancer immunotherapy: more than one plus one? Leuk Res. 2011;35:1136–42.

    Article  CAS  PubMed  Google Scholar 

  10. Thakur A, Schalk D, Sarkar SH, Al-Khadimi Z, Sarkar FH, Lum LG. A Th1 cytokine-enriched microenvironment enhances tumor killing by activated T cells armed with bispecific antibodies and inhibits the development of myeloid-derived suppressor cells. Cancer Immunol Immunother CII. 2012;61:497–509.

    Article  CAS  PubMed  Google Scholar 

  11. Hunder NN, Wallen H, Cao J, Hendricks DW, Reilly JZ, Rodmyre R, et al. Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1. N Engl J Med. 2008;358:2698–703.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Klebanoff CA, Acquavella N, Yu Z, Restifo NP. Therapeutic cancer vaccines: are we there yet? Immunol Rev. 2011;239:27–44.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Rybojad P, Jablonka A, Wilczynska B, Tabarkiewicz J. Surgery decreases number of cells secreting cytotoxic mediators and increases secretion of interleukin 10 in patients with lung cancer. Eur J Surg Oncol J Eur Soc Surg Oncol B Assoc Surg Oncol. 2013;39:1269–77.

    CAS  Google Scholar 

  14. Li MX, Liu XM, Zhang XF, Zhang JF, Wang WL, Zhu Y, Dong J, Cheng JW, Liu ZW, Ma L, Lv Y. Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer J Int Cancer. 2013.

  15. Riedy M. Preventing colorectal cancer. Advance for NPs & PAs. 2013;4:18–21. quiz 22.

    Google Scholar 

  16. de la Cruz-Merino L, Henao Carrasco F, Vicente Baz D, Nogales Fernandez E, Reina Zoilo JJ, Pulido EG, et al. Immune microenvironment in colorectal cancer: a new hallmark to change old paradigms. Clin Dev Immunol. 2011;2011:174149.

    PubMed Central  PubMed  Google Scholar 

  17. 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;153:1687–96.

    CAS  PubMed  Google Scholar 

  18. Schmidt-Wolf GD, Negrin RS, Schmidt-Wolf IG. Activated T cells and cytokine-induced CD3+CD56+ killer cells. Ann Hematol. 1997;74:51–6.

    Article  CAS  PubMed  Google Scholar 

  19. Tang X, Liu T, Zang X, Liu H, Wang D, Chen H, et al. Adoptive cellular immunotherapy in metastatic renal cell carcinoma: a systematic review and meta-analysis. PLoS ONE. 2013;8:e62847.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Stroncek DF, Berger C, Cheever MA, Childs RW, Dudley ME, Flynn P, et al. New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer. J Transl Med. 2012;10:48.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Rosenberg SA. Raising the bar: the curative potential of human cancer immunotherapy. Sci Transl Med. 2012;4:127ps128.

    Article  Google Scholar 

  22. Bonifaz LC, Bonnyay DP, Charalambous A, Darguste DI, Fujii S, Soares H, et al. In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J Exp Med. 2004;199:815–24.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Galea-Lauri J, Wells JW, Darling D, Harrison P, Farzaneh F. Strategies for antigen choice and priming of dendritic cells influence the polarization and efficacy of antitumor T-cell responses in dendritic cell-based cancer vaccination. Cancer Immunol Immunother CII. 2004;53:963–77.

    Article  CAS  PubMed  Google Scholar 

  24. Tu SH, Huang HI, Lin SI, Liu HY, Sher YP, Chiang SK, et al. A novel HLA-A2-restricted CTL epitope of tumor-associated antigen L6 can inhibit tumor growth in vivo. J Immunother. 2012;35:235–44.

    Article  CAS  PubMed  Google Scholar 

  25. Chapuis AG, Thompson JA, Margolin KA, Rodmyre R, Lai IP, Dowdy K, et al. Transferred melanoma-specific CD8+ T cells persist, mediate tumor regression, and acquire central memory phenotype. Proc Natl Acad Sci U S A. 2012;109:4592–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Tietze JK, Wilkins DE, Sckisel GD, Bouchlaka MN, Alderson KL, Weiss JM, et al. Delineation of antigen-specific and antigen-nonspecific CD8(+) memory T-cell responses after cytokine-based cancer immunotherapy. Blood. 2012;119:3073–83.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Prado-Garcia H, Romero-Garcia S, Aguilar-Cazares D, Meneses-Flores M, Lopez-Gonzalez JS. Tumor-induced CD8+ T-cell dysfunction in lung cancer patients. Clin Dev Immunol. 2012;2012:741741.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Wang X, Berger C, Wong CW, Forman SJ, Riddell SR, Jensen MC. Engraftment of human central memory-derived effector CD8+ T cells in immunodeficient mice. Blood. 2011;117:1888–98.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Correspondence to Ying-Xin Xu.

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Du, XH., Liu, HL., Li, L. et al. Clinical significance of immunotherapy with combined three kinds of cells for operable colorectal cancer. Tumor Biol. 36, 5679–5685 (2015). https://doi.org/10.1007/s13277-015-3242-4

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  • DOI: https://doi.org/10.1007/s13277-015-3242-4

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