Phenotypical and functional properties of generated dendritic cells in lung cancer patients

Home/2016, Vol. 4, No. 2/Phenotypical and functional properties of generated dendritic cells in lung cancer patients

Cell and Organ Transplantology. 2016; 4(2):162-166.
DOI: 10.22494/COT.V4I2.63

Phenotypical and functional properties of generated dendritic cells in lung cancer patients

Khranovska N. M., Skachkova O. V., Sovenko V. M., Sydor P. I., Inomistova M. V., Melnyk V. O.
National Cancer Institute of Ministry of Health of Ukraine, Kyiv, Ukraine

Abstract
This study aimed to investigate phenotypical and functional characteristics of dendritic cells (DCs) generated from monocytes of peripheral blood of healthy donors and cancer patients.
Material and methods. DCs were used as natural adjuvants with antitumor vaccine as a part of combined treatment scheme for lung cancer patients. Phenotypical and functional characteristics of DCs were study using flow cytometry and real-time PCR.
Results. We have found that in lung cancer patients generated DCs had moderate level of maturity and demonstrated more pronounced tolerogenic features in contrast to DCs of healthy donors (patients DCs had higher mRNA expression levels of suppressive molecules TGF-β and IDO, and secreted lower amount of bioactive IL-12 protein). Expression of CCR7 gene was particularly on the normal level in DCs of cancer patients which indicates on saving of migratory properties of these cells. Expression level of DC maturity marker CD83 increased after each subsequent vaccine administration, while the levels of TGF-β, IL-10 mRNAs to the end of vaccine therapy course decreased to the level observed in healthy donors DCs.
Conclusion. Thus, the study of biological characteristics of DCs will help to improve and develop the most effective protocols for rational use of DC vaccines. These data indicate the need for further optimization of technologies of DC generation in patients with lung cancer with emphasis on the stimulation of Th1-polarizing properties by increasing cytokine-secreting potential.

Keywords: lung cancer; immunotherapy; dendritic cells; TGF-β; IDO; IL-12

 

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1. Shortman K, Caux С. Dendritic Cell Development: Multiple Pathways to Nature’s. Adjuvants Stem Cells. 1997; 15:409-419. DOI:10.1002/stem.150409
https://doi.org/10.1002/stem.150409
2. Dhodapkar MV, Steinman RM, Krasovsky J, et al. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med. 2001; 193(2):33-38.
https://doi.org/10.1084/jem.193.2.233
3. Figdor CG, de Vries IJ, Lesterhuis WJ, et al. Dendritic cell immunotherapy: mapping the way. Nat Med. 2004; 10(5):475-80.
https://doi.org/10.1038/nm1039
PMid:15122249
4. Kawakami Y, Fujita T, Kudo C, et al. Dendritic cell based personalized immunotherapy based on cancer antigen research. Front Biosci. 2008; 13:1952-58.
https://doi.org/10.2741/2814
PMid:17981682
5. Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer. 2012; 12(4):265-77. doi:10.1038/nrc3258
https://doi.org/10.1038/nrc3258
6. Hettihewa LM. Prolonged expression of MHC class I – peptide expression in bone marrow derived retrovirus transfected matured dendritic cells by continuous centrifugation in the presence of IL-4. Indian J Med Res. 2011; 134(5):672-78.
https://doi.org/10.4103/0971-5916.90993
PMid:22199107 PMCid:PMC3249966
7. Dieckmann D, Schultz E, Ring В, et al. Optimizing the exogenous antigen loading of monocyte-derived dendritic cells. Int Immunol. 2005; 17:621-35.
https://doi.org/10.1093/intimm/dxh243
PMid:15824067
8. Dudek AM, Martin S, Garg AD, et al. Immature, Semi-Mature, and Fully Mature Dendritic Cells: Toward a DC-Cancer Cells Interface That Augments Anticancer Immunity. Front Immunol. 2013; 4:438-52.
https://doi.org/10.3389/fimmu.2013.00438
PMid:24376443 PMCid:PMC3858649
9. Trepiakas R, Pedersenc AE, Svanea IM. Addition of interferon-alpha to a standard maturation cocktail induces CD38 up-regulation and increases dendritic cell function. Vaccine. 2009; 27:2213-19.
https://doi.org/10.1016/j.vaccine.2009.02.015
PMid:19428835
10. Raich-Regue D, Naranjo-Gomez M, Grau-Lopez L, et al. Differential effect of monophosphoryl lipid A and cytokine cocktail as maturation stimuli of immunogenic and tolerogenic dendritic cells for immunotherapy. Vaccine. 2012; 30:378-87.
https://doi.org/10.1016/j.vaccine.2011.10.081
PMid:22085546
11. Richter C, Thieme S, Bandoła J, et al. Generation of Inducible Immortalized Dendritic Cells with Proper Immune Function In Vitro and In Vivo. PLoS One. 2013; 8(4):62621.
https://doi.org/10.1371/journal.pone.0062621
PMid:23626840 PMCid:PMC3633827
12. Sabado R, Bhardwaj N. Cancer immunotherapy: dendritic-cell vaccines on the move. Nature. 2015; 19(519):300-301. doi:10.1038/nature14211
https://doi.org/10.1038/nature14211
13. Anguille S, Bryant ЕС, et al. Dendritic Cells as Pharmacological Tools for Cancer Immunotherapy. Pharmacol Rev. 2015; 67(4):731-753. doi: 10.1124/pr.114.009456.7
14. Park J, Gerber MH, Babensee JE. Phenotype and polarization of autologous t cells by biomaterial-treated dendritic cells. J Biomed Mater Res A. 2015; 103(1):170-84. doi:10.1002/jbm.a.35150.
https://doi.org/10.1002/jbm.a.35150
15. Khranovskaia NN, Grinevich IuA, Potebnia GP, Vorod’eva LI, et al. Vliyanie dendritnokletochnoy autovaktsiny na effektivnost’ lecheniya bol’nykh rakom yaichnika [Effect of dendritic cell autovaccine on the treatment outcome in patients with ovarian cancer]. Vopr Onkol. 2012; 58(6):781-86. [in Russian]
16. Amigorena S, Savina A. Intracellular mechanisms of antigen cross presentation in dendritic cells. Curr Opin Immunol. 2010; 22(1):109-17.
https://doi.org/10.1016/j.coi.2010.01.022
PMid:20171863
17. Baldueva IA, Novik AV, Moiseenko VM. Klinicheskoe issledovanie (II faza) vaktsiny na osnove autologichnykh dendritnykh kletok s immunologicheskim ad”yuvantom u bol’nykh s melanomoy kozhi. [Clinical Study (II phase) of vaccine based on autologous dendritic cells with immunological adjuvants in patients with melanoma]. Vopr Onkologii. 2012; 58(2):212-221. [in Russian]
18. Butterfield LH. Dendritic Cells in Cancer Immunotherapy Clinical Trials: Are We Making Progress? Front Immunol. 2013; 4:454-82.
19. Vacchelli Е, Vitale I, Eggermont A. Dendritic cell-based interventions for cancer therapy. OncoImmunology. 2013; 2(10):25771.
https://doi.org/10.4161/onci.25771
PMid:24286020 PMCid:PMC3841205
20. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010; 363:411-22.
https://doi.org/10.1056/NEJMoa1001294
PMid:20818862
21. Johnson LA, Jackson DG. Cell Traffic and the Lymphatic Endothelium. Ann N Y Acad Sci. 2008; 1131:119-33.
https://doi.org/10.1196/annals.1413.011
PMid:18519965
22. Gollmann G, Neuwirt H, Tripp CH, et al. Sphingosine-1-phosphate receptor type-1 agonism impairs blood dendritic cell chemotaxis and skin dendritic cell migration to lymph nodes under inflammatory conditions. Int Immunol. 2008; 18(1):49-54.
https://doi.org/10.1093/intimm/dxn050
23. Fucikova J, Kralikova P, Fialova A, et al. Human tumor cells killed by anthracyclines induce a tumor-specific immune response. Cancer Res. 2011; 71(14):4821-33. doi: 10.1158/0008-5472.CAN-11-0950
https://doi.org/10.1158/0008-5472.CAN-11-0950
24. Navabi H, Jasani B, Reece A, et al. A clinical grade poly I:C-analogue (Ampligen) promotes optimal DC maturation and Th1-type T cell responses of healthy donors and cancer patients in vitro. Vaccine. 2009; 27(1):107-15. doi: 10.1016/j.vaccine.2008.10.024
https://doi.org/10.1016/j.vaccine.2008.10.024
25. Kalinskia P, Okada H. Polarized dendritic cells as cancer vaccines: Directing effector-type T cells to tumors. Seminars in Immunology. 2010; 22:173-82.
https://doi.org/10.1016/j.smim.2010.03.002
PMid:20409732 PMCid:PMC2892234
26. Mailliard RB, Wankowicz-Kalinska A, Cai Q, et al. α-Type-1 Polarized Dendritic Cells: A Novel Immunization Tool with Optimized CTL-inducing Activity. Cancer Resaerch. 2004; 64:5934-37.
https://doi.org/10.1158/0008-5472.CAN-04-1261
PMid:15342370
27. Khranovskaia NN, Skachkova OV, Svergun NN. Fenotipicheskaya i funktsional’naya kharakteristika generirovannykh in vitro dendritnykh kletok cheloveka posle aktivatsii lipopolisakharidom i interferonom-ɑ [Phenotypic and functional characterization of dendritic cells generated in vitro after activation by human lipopolysaccharide and interferon-ɑ]. Іmunologіya ta alergologіya – Immunology and allergology. 2013; 4:72-76. [in Russian]
28. Khranovskaia NN, Kryachok IA, Ganul VL, et al. Razrabotka, obosnovanie i otsenka effektivnosti protivoopukholevoy vaktsinoterapii na osnove dendritnykh kletok u bol’nykh so zlokachestvennymi novoobrazovaniyami [Elaboration, rationale and clinical benefit of antitumor vaccine therapy based on dendritic cells for patients with malignant neoplasms]. Klіnіchna onkologіya – Clinical Oncology. 2014; 2(14):62-70. [in Russian]
29. Chernykh EP, Leplina OYu, Tyrinova TV, et al. Protivoopukholevaya aktivnost’ dendritnykh kletok zdorovykh donorov i bol’nykh s opukholyami golovnogo mozga [The antitumor activity of dendritic cells from healthy donors and patients with brain tumors]. Med immunologiya – Med Immunology. 2010; 12(3):199-206.
https://doi.org/10.15789/1563-0625-2010-3-199-206
30. Chiang CL, Maier DA, Kandalaft LE, et al. Optimizing parameters for clinical-scale production of high IL-12 secreting dendritic cells pulsed with oxidized whole tumor cell lysate. J Transl Med. 2011; 9:198-230.
https://doi.org/10.1186/1479-5876-9-198
PMid:22082029 PMCid:PMC3283529
31. Draube A, Klein-Gonzalez N, Mattheus S, et al. Dendritic Cell Based Tumor Vaccination in Prostate and Renal Cell Cancer: A Systematic Review and Meta-Analysis. PLoS One. 2011; 6(4):18801. doi:10.1371/journal.pone.0018801
https://doi.org/10.1371/journal.pone.0018801
32. Pletinckx К, Stijlemans В, Pavlovic V, et al. Similar inflammatory DC maturation signatures induced by TNF or Trypanosoma brucei antigens instruct default Th2-cell responses . Eur J Immunol. 2011; 41:3479–94. doi:10.1002/eji.201141631
https://doi.org/10.1002/eji.201141631
33. Motta JM, Rumjanek VM. Sensitivity of Dendritic Cells to Microenvironment Signals. J Immunol Res. 2016. Retrieved from http://dx.doi.org/10.1155/2016/4753607
https://doi.org/10.1155/2016/4753607
34. Raker VK, Domogalla MP, Steinbrink K. Tolerogenic Dendritic Cells for Regulatory T Cell Induction in Man. Front Immunol. 2015; 6:569. doi:10.3389/fimmu.2015.00569
https://doi.org/10.3389/fimmu.2015.00569
35. Manicassamy S, Pulendran B. Dendritic cell control of tolerogenic responses. Immunol Rev. 2011; 241(1):206-27. doi:10.1111/j.1600-065X.2011.01015.x
https://doi.org/10.1111/j.1600-065X.2011.01015.x
36. Gordon JR, Ma Y, Churchman L, et al. Regulatory Dendritic Cells for Immunotherapy in Immunologic Diseases. Front Immunol. 2014; 5:1-19. doi:10.3389/fimmu.2014.00007
https://doi.org/10.3389/fimmu.2014.00007

Khranovska NM, Skachkova OV, Sovenko VM, Sydor PI, Inomistova MV, Melnyk VO. Phenotypical and functional properties of generated dendritic cells in lung cancer patients. Cell and Organ Transplantology. 2016; 4(2):162-166. doi:10.22494/cot.v4i2.63

 

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