IN VITRO STIMULATION OF ANTITUMOR CYTOTOXIC ACTIVITY OF MONONUCLEAR CELLS FROM COLORECTAL CANCER PATIENTS
https://doi.org/10.15789/1563-0625-2013-3-235-246
Abstract
Abstract. In present study, we investigated the in vitro ability of autologous dendritic cells loaded with tumor lysate antigens to stimulate cytotoxic and secretory activity of effector cells from patients with colorectal cancer. To this purpose, we generated antigen-primed dendritic cells (DS) derived from adherent fraction of peripheral blood mononuclear cells (PBMSc) obtained from patients with colorectal cancer. The DCs were then cocultured with non-adherent mononuclear cells, either in presence of IL-12 and IL-18, or without cytokines. The modulation efficiency was assessed as cytotoxic activity of mononuclear cells towards autologous tumor cells, production of IFNγ, IL-2, IL-4 and the number of perforin-, granzyme B-containing cells. We have demonstrated the ability of dendritic cells to stimulate the in vitro antitumor cytotoxic and secretory activity of effector cells in culture. A combination of dendritic cells with IL-12 and IL-18 is shown to enhance their effects in the mononuclear cells culture, as evidenced by increased percentage of dead autologous tumor cells, higher numbers of perforin(+), granzyme B(+) lymphocytes, and increased production of IFNγ, IL-2 increased.
About the Authors
V. V. Kurilin
Research Institute of Clinical Immunology, Siberian Branch, Russian Academy of Medical Sciences, Novosibirsk
Russian Federation
Russian Federation
PhD (Medicine), Senior Research Associate, Laboratory of Molecular Immunology
Yu. N. Khantakova
Research Institute of Clinical Immunology, Siberian Branch, Russian Academy of Medical Sciences, Novosibirsk
Russian Federation
PhD Candidate
Russian Federation
PhD Candidate
I. A. Obleukhova
Research Institute of Clinical Immunology, Siberian Branch, Russian Academy of Medical Sciences, Novosibirsk
Russian Federation
Russian Federation
Research Associate, Laboratory of Molecular Immunology
Yu. A. Shevchenko
Research Institute of Clinical Immunology, Siberian Branch, Russian Academy of Medical Sciences, Novosibirsk
Russian Federation
Russian Federation
PhD (Biology), Research Associate, Laboratory of Molecular Immunology
E. V. Kulikova
Research Institute of Clinical Immunology, Siberian Branch, Russian Academy of Medical Sciences, Novosibirsk
Russian Federation
PhD Candidate
Russian Federation
PhD Candidate
V. K. Yakushenko
Clinical Hospital No. 1, Novosibirsk
Russian Federation
Russian Federation
City Center of Coloproctology
PhD, MD (Medicine), Chief, Second Surgical Department
A. V. Sokolov
City Clinical Hospital No. 1, Novosibirsk
Russian Federation
Chief, Second Department of Oncology
Russian Federation
Chief, Second Department of Oncology
S. V. Sennikov
Research Institute of Clinical Immunology, Siberian Branch, Russian Academy of Medical Sciences, Novosibirsk
Russian Federation
Russian Federation
PhD, MD (Medicine), Professor, Chief, Laboratory of Molecular Immunology
References
1. Каралкин П.А., Лупатов А.Ю., Ярыгин К.Н. Эндоцитоз микро- и наноразмерных частиц дендритными клетками человека в культуре // Биологические мембраны. – 2009. – № 5. – C. 394-400. Karalkin P.A., Lupatov A.Yu., Yarygin K.N. Endotsitoz mikro- i nanorazmernykh chastits dendritnymi kletkami cheloveka v kul`ture [Endocytosis of micro- and nanosized particles in vitro by human dendritic cells]. Biologicheskie membrany – Membrane and Cell Biology. Biochemistry (Moscow) suppl. Series A, 2009, no. 5, pp. 394-400.
2. Злокачественные новообразования в России в 2010 году (заболеваемость и смертность) / Под редакцией В.И. Чиссова, В.В. Старинского, Г.В. Петровой. – М.: ФГБУ «МНИОИ им. П.А. Герцена» Минздравсоцразвития России, 2012. – 260 с. Zlokachestvennye novoobrazovaniya v Rossii v 2010 godu (zabolevaemost` i smertnost`). Pod redaktsiey Chissova V.I., Starinskogo V.V., Petrovoy G.V. [Malignancies in Russia in 2010 (morbidity and mortality). Eds.: Chissov V.I., Starinsky V.V., Petrova G.V.]. Moscow, FGBU «MNIOI after P.A. Hertzen» Minzdravsocrazvitiya Rossii – FGBU «MNIOI after P.A. Hertzen» Minzdravsocrazvitiya Russia, 2012. 260 p.
3. Andrade F., Roy S., Nicholson D., Thornberry N., Rosen A., Casciola-Rosen L. Granzyme B directly and efficiently cleaves several downstream caspasesubstrates: implications for CTLre-induced apoptosis. Immunity, 1998, vol. 8, no. 4, pp. 451-460.
4. Cammarota R., Bertolini V., Pennesi G., Bucci E.O’, Gottardi O., Garlanda C., Laghi L., Barberis M.C., Sessa F., Noonan D.M., Albini A. The tumor microenvironment of colorectal cancer: stromal TLR-4 expression as a potential prognostic marker. Journal of Translational Medicine, 2010, vol. 8, pp. 112-128.
5. Chiang C.L.-L., Benencia F., Coukos G. Whole Tumor Antigen Vaccines. Semin. Immunol., 2010, vol. 22, no. 3, pp. 132-143.
6. Colotta F., Allavena P., Sica A., Garlanda C., Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis, 2009, vol. 7, pp. 1073-1081.
7. De Jong E.C., Smits H.H., Kapsenberg M.L. Dendritic cell-mediated T cell polarization. Springer Semin. Immun., 2004, vol. 26, pp. 289-307.
8. Deschoolmeester V., Baay M., Marck E.V., Weyler J., Vermeulen P., Lardon F., Vermorken J.B. Tumor infiltrating lymphocytes: an intriguing player in the survival of colorectal cancer patients. BMC Immunology, 2010, vol. 11, pp. 1471-2172.
9. Gracie J.A., Robertson S.E., McInnes I.B. Interleukin-18. J. Leukoc. Biol., 2003, vol. 73, pp. 213-224.
10. Hoves S., Sutton V.R., Haynes N.M., Hawkins E.D., Fern ndez Ruiz D., Baschuk N., Sedelies K.A., Schnurr M., Stagg J., Andrews D.M., Villadangos J.A., Trapani J.A. A critical role for granzymes in antigen cross-presentation through regulating phagocytosis of killed tumor cells. J. Immunol., 2011, vol. 187, no. 3, pp. 1166-1175.
11. Jarnjak-Jankovic S., Hammerstad H., S b e-Larssen S., Kvalheim G., Gaudernack G. A full scale comparative study of methods for generation of functional dendritic cells for use as cancer vaccines. BMC Cancer, 2007, vol. 7, no. 119, pp. 2407-7-119.
12. Johanna E.A. Portielje, Jan Willem Gratama, Heidi H . van Ojik, Gerrit Stoter, Wim H.J. Kruit IL-12: a promising adjuvant for cancer vaccination. Cancer Immunol. Immunother, 2003, vol. 52, pp. 133-144.
13. Keefe D., Shi L., Feske S., Massol R., Navarro F., Kirchhausen T., Lieberman J. Perforin triggers a plasma membrane-repair response that facilitates CTL induction of apoptosis. Immunity, 2005, vol. 23, no. 3, pp. 249-262.
14. Liu K., Caldwell S.A., Greeneltch K.M., Yang D., Abrams S.I. CTL Adoptive Immunotherapy Concurrently Mediates Tumor Regression and Tumor Escape. J. Immunol., 2006, vol. 176, pp. 3374-3382.
15. Malmberg K.-J., Levitsky V., Norell H., de Matos C.T., Carlsten M., Schedvins K., Rabbani H., Moretta A., Söderström K., Levitskaya J., Kiessling R. IFN-γ protects short-term ovarian carcinoma cell lines from CTL lysis via a CD94/NKG2A-dependent mechanism. J. Clin. Invest., 2002, vol. 110, pp. 1515-1523.
16. Munk R.B., Sugiyama K., Ghosh P., Sasaki C.Y., Rezanka L., Banerjee K., Takahashi H., Sen R., Longo D.L. Antigen-independent IFN-γ production by human naive CD4+ T cells activated by IL-12 plus IL-18. Plos One, 2011, vol. 6, no. 5, p. 18553.
17. Nakanishi K., Yoshimoto T., Tsutsui H., Okamura H. Interleukin-18 regulates both Th1 and Th2 responses. Annu. Rev. Immunol., 2001, vol. 19, pp. 423-474.
18. Nersting J., Svenson M., Andersen V., Bendtzen K. Maturation of human dendritic cells by monocyteconditioned medium is dependent upon trace amounts of lipopolysaccharide inducing tumour necrosis factor α. Immunology Letters, 2003, vol. 89, pp. 59-65.
19. Rousalova I., Krepela E. Granzyme B-induced apoptosis in cancer cells and its regulation (Review). International Journal of Oncology, 2010, vol. 37, pp. 1361-1378.
20. Thomas D.A., Scorrano L., Putcha G.V., Korsmeyer S.J., Ley T.J. Granzyme B can cause mitochondrial depolarization and cell death in the absence of BID, BAX, and BAK. Proc Natl Acad Sci USA, 2001, vol. 98, no. 26, pp. 14985-14990.
21. Trambas C.M., Griffiths G.M. Delivering the kiss of death. Review. Nat. Immunol., 2003, vol. 4, no. 5, pp. 399-403.
22. Zhou L., Chong M.M.W., Littman D.R. Plasticity of CD4+ T Cell Lineage Differentiation. Immunity, 2009, vol. 30, pp. 646-655.
Review
For citations:
Kurilin V.V., Khantakova Yu.N., Obleukhova I.A., Shevchenko Yu.A., Kulikova E.V., Yakushenko V.K., Sokolov A.V., Sennikov S.V. IN VITRO STIMULATION OF ANTITUMOR CYTOTOXIC ACTIVITY OF MONONUCLEAR CELLS FROM COLORECTAL CANCER PATIENTS. Medical Immunology (Russia). 2013;15(3):235-246. (In Russ.) https://doi.org/10.15789/1563-0625-2013-3-235-246
Views:
1047
Email this article 