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01-12-2016 | Original Article

Dendritic cells loading autologous tumor lysate promote tumor angiogenesis

Authors: Yi Yang, Jing Lu, Hangfan Liu, Guoguo Jin, Ruihua Bai, Xiang Li, Dongyu Wang, Jimin Zhao, Youtian Huang, Kangdong Liu, Ying Xing, Ziming Dong

Published in: Tumor Biology | Issue 12/2016

Abstract

Dendritic cells (DC) have been exploited for vaccination against cancer for years. DC loading autologous tumor lysate (ATL-DC) have been assessed in ongoing clinical trials, but frequently do not meet expectation. In this study, we found that mice immunized with ATL-DC induced less protective anti-tumor effect than immunized with DC alone. The percentage of CD8⁺ T cells and the lysis efficiency of CTLs to auto tumor cells in ATL-DC vaccination group was less than that of DC group. Moreover, vaccination of mice with ATL-DC also promoted tumor angiogenesis by analyzing the CD31 positive microvessel density and hemoglobin content of tumor specimens. Human umbilical vein endothelial cells (HUVEC) have been proved effective in the anti-angiogenesis immunity against cancer. However, in the following research we found that the anti-tumor effect was attenuated while immunized mice with HUVEC combined with ATL-DC (HUVEC + ATL-DC). Furthermore, immunized mice with HUVEC + ATL-DC profoundly increased the tumor angiogenesis by analyzing the microvessel density and hemoglobin content of tumor specimens. These data suggest that vaccination using ATL-DC antagonized HUVEC induced anti-angiogenesis effect. Our research for the first time indicated that ATL-DC have the potential to promote the process of tumor angiogenesis in vivo. As vaccines based on DC loading autologous tumor lysate have been used in clinical, this find warned that the safety of this kind of vaccine should be taken into consideration seriously.

Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice—i. morphology, quantitation, tissue distribution (reprinted from j exp med, vol 137, pg 1142-1162, 1973. J Immunol. 2007;178:5–25.PubMed

Constantino J, Gomes C, Falcao A, Cruz MT, Neves BM. Antitumor dendritic cell-based vaccines: lessons from 20 years of clinical trials and future perspectives. Transl Res. 2016;168:74–95.CrossRefPubMed

Gu X, Erb U, Büchler MW, Zöller M. Improved vaccine efficacy of tumor exosome compared to tumor lysate loaded dendritic cells in mice. Int J Cancer. 2015;136:E74–84.CrossRefPubMed

Lasky JL, Panosyan EH, Plant A, Davidson T, Yong WH, Prins RM, Liau LM, Moore TB. Autologous tumor lysate-pulsed dendritic cell immunotherapy for pediatric patients with newly diagnosed or recurrent high-grade gliomas. Anticancer Res. 2013;33:2047–56.PubMedPubMedCentral

Rainone V, Martelli C, Ottobrini L, Biasin M, Texido G, Degrassi A, Borelli M, Lucignani G, Trabattoni D, Clerici M: Immunological characterization of whole tumour lysate-loaded dendritic cells for cancer immunotherapy (vol 1, e0146622, 2016). Plos One 2016;11

Frenzel H, Pries R, Brocks CP, Jabs WJ, Wittkopf N, Wollenberg B. Decreased migration of myeloid dendritic cells through increased levels of c-reactive protein. Anticancer Res. 2007;27:4111–5.PubMed

Lu J, Liu KD, Zhao JM, Zhao J, Ma JF, Yang HY, Huang YT, Qin ZZ, Bai RH, Jiang LL, Lv FS, Li P, Yan WH, Zhao MY, Dong ZM. Vegf-a not ang2 mediates endothelial-like differentiation of immature dcs by erk1/2 signaling in the microenvironment of human colon adenocarcinoma. Int J Oncol. 2011;38:1579–88.PubMed

Gottfried E, Kreutz M, Haffner S, Holler E, Iacobelli M, Andreesen R, Eissner G. Differentiation of human tumour-associated dendritic cells into endothelial-like cells: an alternative pathway of tumour angiogenesis. Scand J Immunol. 2007;65:329–35.CrossRefPubMed

Azoitei N, Becher A, Steinestel K, Rouhi A, Diepold K, Genze F, Simmet T, Seufferlein T. Pkm2 promotes tumor angiogenesis by regulating hif-1alpha through nf-kappab activation. Mol Cancer. 2016;15:3.CrossRefPubMedPubMedCentral

10.

Okaji Y, Tsuno NH, Saito S, Yoneyama S, Tanaka M, Nagawa H, Takahashi K. Vaccines targeting tumour angiogenesis—a novel strategy for cancer immunotherapy. European Journal of Surgical Oncology (EJSO). 2006;32:363–70.CrossRef

11.

Wei YQ, Wang QR, Zhao X, Yang L, Tian L, Lu Y, Kang B, CJ L, Huang MJ, Lou YY, Xiao F, He QM, Shu JM, Xie XJ, Mao YQ, Lei S, Luo F, Zhou LQ, Liu CE, Zhou H, Jiang Y, Peng F, Yuan LP, Li Q, Wu Y, Liu JY. Immunotherapy of tumors with xenogeneic endothelial cells as a vaccine. Nat Med. 2000;6:1160–6.CrossRefPubMed

12.

ML X, Xing Y, Zhou L, Yang X, Yao WJ, Xiao W, Ge CY, Ma YJ, Yang J, Wu J, Cao RY, Li TM, Liu JJ. Improved efficacy of therapeutic vaccination with viable human umbilical vein endothelial cells against murine melanoma by introduction of ok432 as adjuvant. Tumor Biol. 2013;34:1399–408.CrossRef

13.

Lutz MB, Suri RM, Niimi M, Ogilvie AL, Kukutsch NA, Rossner S, Schuler G, Austyn JM. Immature dendritic cells generated with low doses of gm-csf in the absence of il-4 are maturation resistant and prolong allograft survival in vivo. Eur J Immunol. 2000;30:1813–22.CrossRefPubMed

14.

Benencia F, Sprague L, McGinty J, Pate M, Muccioli M. Dendritic cells the tumor microenvironment and the challenges for an effective antitumor vaccination. J Biomed Biotechnol. 2012;2012:1–15.CrossRef

15.

Prins RM, Wang XY, Soto H, Young E, Lisiero DN, Fong B, Everson R, Yong WH, Lai A, Li G, Cloughesy TF, Liau LM. Comparison of glioma-associated antigen peptide-loaded versus autologous tumor lysate-loaded dendritic cell vaccination in malignant glioma patients. J Immunother. 2013;36:152–7.CrossRefPubMedPubMedCentral

16.

Ovali E, Dikmen T, Sonmez M, Yilmaz M, Unal A, Dalbasti T, Kuzeyli K, Erturk M, Omay SB. Active immunotherapy for cancer patients using tumor lysate pulsed dendritic cell vaccine: a safety study. J Exp Clin Cancer Res. 2007;26:209–14.PubMed

17.

Orsini E, Guarini A, Chiaretti S, Mauro FR, Foa R. The circulating dendritic cell compartment in patients with chronic lymphocytic leukemia is severely defective and unable to stimulate an effective t-cell response. Cancer Res. 2003;63:4497–506.PubMed

18.

Lu J, Zhao J, Zhao JM, Ma JF, Liu KD, Yang HY, Huang YT, Qin ZZ, Bai RH, Li P, Yan WH, Zhao MY, Dong ZM. Vegf-a-induced immature dcs not mature dcs differentiation into endothelial-like cells through erk1/2-dependent pathway. Cell Biochem Funct. 2011;29:294–302.CrossRefPubMed

19.

Lu J, Zhao JM, Liu KD, Zhao J, Yang HY, Huang YT, Qin ZZ, Bai RH, Li P, Ma JF, Yan WH, Zhao MY, Dong ZM. Mapk/erk1/2 signaling mediates endothelial-like differentiation of immature dcs in the microenvironment of esophageal squamous cell carcinoma. Cell Mol Life Sci. 2010;67:2091–106.CrossRefPubMed

20.

Lu J, Bai RH, Qin ZZ, Zhang YY, Zhang XY, Jiang YA, Yang HY, Huang YT, Li G, Zhao MY, Dong ZM. Differentiation of immature dcs into endothelial-like cells in human esophageal carcinoma tissue homogenates. Oncol Rep. 2013;30:739–44.PubMed

21.

Jin G, Zhao J, Yang Y, Liu K, Jiang Y, Zhang X, Zhang Y, Huang Y, Lu J, Dong Z: Jak/stat3 signaling pathway mediates endothelial-like differentiation of immature dendritic cells. Oncol Lett 2015

22.

Conejo-Garcia JR, Benencia F, Courreges M-C, Kang E, Mohamed-Hadley A, Buckanovich RJ, Holtz DO, Jenkins A, Na H, Zhang L, Wagner DS, Katsaros D, Caroll R, Coukos G. Tumor-infiltrating dendritic cell precursors recruited by a β-defensin contribute to vasculogenesis under the influence of vegf-a. Nat Med. 2004;10:950–8.CrossRefPubMed

23.

Weidner N. Angiogenesis as a predictor of clinicaloutcome in cancer patients. Hum Pathol. 2000;31:403–5.CrossRefPubMed

24.

Mu X, Sang Y, Fang C, Shao B, Yang L, Yao K, Zhao X, Gou J, Wei Y, Yi T, Wu Y, Zhao X: Immunotherapy of tumors with human telomerase reverse transcriptase immortalized human umbilical vein endothelial cells. Int J Oncol 2015

25.

Chen XY, Zhang W, Zhang W, Wu S, Bi F, JJ S, Tan XY, Liu JN, Zhang J. Vaccination with viable human umbilical vein endothelial cells prevents metastatic tumors by attack on tumor vasculature with both cellular and humoral immunity. Clin Cancer Res. 2006;12:5834–40.CrossRefPubMed

26.

Okaji Y, Tsuno NH, Kitayama J, Saito S, Takahashi T, Kawai K, Yazawa K, Asakage M, Hori N, Watanabe T, Shibata Y, Takahashi K, Nagawa H. Vaccination with autologous endothelium inhibits angiogenesis and metastasis of colon cancer through autoimmunity. Cancer Sci. 2004;95:85–90.CrossRefPubMed

27.

Riboldi E, Musso T, Moroni E, Urbinati C, Bernasconi S, Rusnati M, Adorini L, Presta M, Sozzani S. Cutting edge: proangiogenic properties of alternatively activated dendritic cells. J Immunol. 2005;175:2788–92.CrossRefPubMed

28.

Kishuku M, Nishioka Y, Abe S, Kishi J, Ogino H, Aono Y, Azuma M, Kinoshita K, Batmunkh R, Makino H, Ranjan P, Minakuchi K, Sone S. Expression of soluble vascular endothelial growth factor receptor-1 in human monocyte-derived mature dendritic cells contributes to their antiangiogenic property (vol 183, pg 8176, 2009. J Immunol. 2010;185:2630.CrossRef

29.

Curiel TJ, Cheng P, Mottram P, Alvarez X, Moons L, Evdemon-Hogan M, Wei S, Zou LH, Kryczek I, Hoyle G, Lackner A, Carmeliet P, Zou WP. Dendritic cell subsets differentially regulate angiogenesis in human ovarian cancer. Cancer Res. 2004;64:5535–8.CrossRefPubMed

30.

Sozzani S, Rusnati M, Riboldi E, Mitola S, Presta M. Dendritic cell-endothelial cell cross-talk in angiogenesis. Trends Immunol. 2007;28:385–92.CrossRefPubMed

Title: Dendritic cells loading autologous tumor lysate promote tumor angiogenesis
Authors: Yi Yang
Jing Lu
Hangfan Liu
Guoguo Jin
Ruihua Bai
Xiang Li
Dongyu Wang
Jimin Zhao
Youtian Huang
Kangdong Liu
Ying Xing
Ziming Dong
Publication date: 01-12-2016
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 12/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-016-5312-7

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