IMMUNE NETWORK

The Korean Association of Immunobiologists (대한면역학회)
권호 표지

Mechanism of Differential Ag-specific Immune Induction by Different Tumor Cell Lysate Pulsed DC

종양 세포 용해액에 따른 수지상세포 유도 항원 특이 면역반응 차이의 기전 연구

  • Lee, Kang-Eun (The Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Shon, Hye-Jin (The Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Myung-Joo (The Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Baek, So-Young (The Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Hyun-Ah (The Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 이강은 (성균관대학교 의과대학 삼성서울병원 암센터) ;
  • 손혜진 (성균관대학교 의과대학 삼성서울병원 암센터) ;
  • 김명주 (성균관대학교 의과대학 삼성서울병원 암센터) ;
  • 백소영 (성균관대학교 의과대학 삼성서울병원 암센터) ;
  • 이현아 (성균관대학교 의과대학 삼성서울병원 암센터)
  • Published : 2006.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Tumor cell lysate has been considered as a preferential antigen source for the therapeutic dendritic cell pulsing. Our experiences with in vivo study with animal tumor model indicate the tumor cell lysate dependent differential effect of DC therapy. Our previous data show that MC38 lysate pulsed-DC induced stronger ag-specific immunity than CT26 lysate pulsed-DC in vitro. In this study we tried to reveal the mechanism for differential induction of ag-specific immunity of different colon cancer cell lysate pulsed-DCs. Methods: MC38 and CT26 cell lines were prepared as lysate by freezing-thawing procedure. Tumor cell antigenicity was confirmed by detecting the surface expression of MHC I/II & B7.1/2 molecules. IL-10, IL-12 and TGF-beta in the tumor cell lysate were detected by ELISA and the presence of heat shock proteins were analysed by western blotting. Results: The secretion of IL-10, a immune-inhibitory cytokine was about 470% higher in CT26 lysate than in MC38. Hsp 70 was detected only in the MC38 lysate but not in the CT26. On the other hand, Hsp 60 and 90 expression were not different in two colon cancer cell lysates. Conclusion: In two different colon cancer cell lysate, immune inhibitory IL-10 (higher in CT26) and Hsp70 (MC38 superiority) were differentially expressed. These data indicate that higher agspecific immunity induction by MC38 lysate pulsed-DC may due to the expression of hsp70 and lower secretion of IL-10, a immune-inhibitory cytokine than CT26 lysate. The significance of other cytokine and the surface marker expression will be discussed.

Keywords

References

  1. 배용수: 수지상세포를 이용한 암치료제 개발현황 및 전망. Tissue Engineering and Regenerative Medicine 2;251-263, 2005
  2. Nestle F: Dendritic cell vaccination for cancer therapy. Oncogene 19;6673-6679, 2000 https://doi.org/10.1038/sj.onc.1204095
  3. Banchereau J, Palucka K: Karolina Palucka. Dendritic cells as therapeutic vaccines against cancer. Nat Immunol 5;296- 306, 2005 https://doi.org/10.1038/nri1592
  4. 이영준, 김명주, 인소희, 최옥미, 백소영, 권영도, 이현아: 동종 종양 세포 용해액을 이용한 수지상 세포 항암 백신의 흑색종 폐암 전이 모델에서의 효과 연구 Imrnune Network 5;163-171, 2005 https://doi.org/10.4110/in.2005.5.3.163
  5. Steinman RM: The dendritic cell system and its role in irnmunogenicity. Annu Rev Immunol 9;271-296, 1991 https://doi.org/10.1146/annurev.iy.09.040191.001415
  6. Paglia P, Chiodoni C, Rodolfo M, Colombo MP: Murine dendritic cells loaded in vitro with soluble protein prime cytotoxic T lymphocytes aginsttumor antigen in vivo. J Exp Mcd 183;317 -322, 1996 https://doi.org/10.1084/jem.183.1.317
  7. Brossart P, Goldrath AW, Butz EA, Martin S, Bevan MJ: Virus mediated delivery of antigenic epitopes into dendritic cells as a means to induced CTL. J Immunol 158;3270-3276, 1997
  8. Brossart P, Becan MJ: Presentation of exogenous protein adtigens on major histocompartibility complex class I molecules by dendritic cells: pathway of presentation and regulation by cytokines. Blood 90;1594-1599, 1997
  9. Banchereau K, Steinman RM: Dendritic cells and th control of immunity. Nature 392;245-252, 1998
  10. Cella M, Sallusto F, Lanzavecchia A: Origin, maturation and antigen presenting function of dendritic cells Curr Opin Irnmunol 9;10-16, 1997 https://doi.org/10.1016/S0952-7915(97)80153-7
  11. Porgador A, Gilboa E: Bone marrow generated dendritic cells pulsed with a class I restricted peptide are potent inducers of cytotoxic T lymphocytes. J Exp Med 182;255-260, 1995 https://doi.org/10.1084/jem.182.1.255
  12. Zitvogel L, Mayordomo JI, Tjandrawan T, DeLeo AB, Clarke MR, Lotze MT: Therapy of murine tumors with tumor peptide pulsed dendritic cells: dependent on T cells, B7 cos timulation, and T helper cell 1 associated cytokines. J Exp Med 183;87-97, 1996 https://doi.org/10.1084/jem.183.1.87
  13. Bevan MJ: Cross priming for a secondary cytotoxic response to minor H antigen with H-2 congenic cells which do not cross react in the cytotoxic assay. J Exp Med 143;1283-1288, 1976 https://doi.org/10.1084/jem.143.5.1283
  14. Huang AY, Golumbek P, Ahmadzadeh M, Jaffee E, Pardoll D, Levitsky H: Role of bone marrow derived cells in presenting MHC class I resticted tumor antigens. Science 264; 961-965, 1994 https://doi.org/10.1126/science.7513904
  15. Reis e Sousa, Germain R: Major histocompatibility complex class I presentation of peptides derived from soluble exogenous antigen by a subset of cellseagaged in phagocytosis. J Exp Med 182;841-851, 1995 https://doi.org/10.1084/jem.182.3.841
  16. Norbury CC, Chambers BJ, Prescott AR, Ljunggren Hg, Watts C: Constitutive macropinocytosis allows TAP-dependent presentation of exogenous antigen on class I MHC molecules by bone marrow derived dendritic cells. Eur J Immunol 27; 280-288, 1997 https://doi.org/10.1002/eji.1830270141
  17. Carbone FR, Kurts C, Bennett SE, Miller JF, Heatth WR: Cross-presentation: a general mechanism for CTL immunity and tolerance. Immunol Today 19;368-373, 1998 https://doi.org/10.1016/S0167-5699(98)01301-2
  18. 박민호, 이창석, 조문형, 한철, 고양석, 김정철, 윤정한, 정갈영 종, 남종희: 암 태아성 항원 탭타이드로 부가된 수지상세포를 이용한 특이 세포독성 T 세포의 유도. 대한외과학회지 69; 359-366, 2005
  19. Figdor C, Vries I, Lesterhuis W, Melief C: Dendritic cell immunotherapy: mapping the way. Nat Med 10;475-480, 2004 https://doi.org/10.1038/nm1039
  20. Nair S, Snyder D, Rouse B, Gilboa E. David Snyder, Barry T. Rouse, Eli Gilboa: Regression of tumors in mice vaccinated with professional antigen presenting cells pulsed with tumor extracts. Int J Cancer 70;706-715, 1997 https://doi.org/10.1002/(SICI)1097-0215(19970317)70:6<706::AID-IJC13>3.0.CO;2-7
  21. van Eden W, van dcr Zee R, Prakken B: Heat shock proteins induce T cell regulation of chronic inflammation. Nat Immunol 5;318-330, 2005 https://doi.org/10.1038/nri1593
  22. Kaufmann SHE: Heat shock proteins immune resposnse. Irnmonol. Today 11;129-136, 1990 https://doi.org/10.1016/0167-5699(90)90050-J
  23. Beackmann RP, Lovett M, Welch WJ: Examining the function and regulation of Hsp 70 in cells subjected th meta bolic stress. J Cell Biol 117;1137-1150, 1992 https://doi.org/10.1083/jcb.117.6.1137
  24. Nakamura K, Rokutan K, Marni N: Induction of heat shock proteins and their implication in protection against erhanolinduced damage in cultured guinea pig gastric mucosal cells. gastroenterology 101;161-169, 1991 https://doi.org/10.1016/0016-5085(91)90473-X
  25. VanBuskirt AM, DeNagel DC, Guagliardi LE: Cellular and subcellular distribution of PBP 72/74, a pepride binding protein that playa role in antigen processing. K immunol 146; 500-506, 1991
  26. Lindquist S, Craig EA: The heat shock proteins. Anni Rev Genet 22;631-677, 1988 https://doi.org/10.1146/annurev.ge.22.120188.003215
  27. 이현아, 최광민, 백소영, 이홍기, 정철원: 수지상세포를 이용한 항암 면역 치료: 생쥐 신장암 모델을 이용한 연구. Immune Network 4;44-52, 2004 https://doi.org/10.4110/in.2004.4.1.44
  28. 이석재, 김명주, 인소희, 백소영, 이현아: 폐암의 면역세포 치료: 동물 모델에서 수지상 세포를 이용한 adjuvant therepy 가능성 연구. Immune Network 5;36-44, 2005 https://doi.org/10.4110/in.2005.5.1.36
  29. Yoon(Lee) H, Singh K, Ratner S, Reiners JJ Jr: Phorbol ester effets on splenic lymphocyte composition and cytotoxic T cell activities of SSIN mice: a strain deficient in CD8+ T cells. Carcinogenesis 17;2617- 2624, 1996 https://doi.org/10.1093/carcin/17.12.2617
  30. Milani V, Noessner E, Ghose S, Kuppner M, Ahrens B, Scharner A, Gastpar R, Isseis RD: Heat shock protein 70: role in antigen presentation and immune stimulation. Int J Hyperthermia 18;563-575, 2002 https://doi.org/10.1080/02656730210166140
  31. Multhoff G: Activation of natural killer cells by heat shock proteins70. Int J Hyperthermia 18;576-585, 2002 https://doi.org/10.1080/0265673021000017109
  32. Manjili MH, Wang XY, Park J, Macdonald IJ, Li Y, van Schie R, Subjeck JR: Cancer immunotherapy: stress proteins and hyperthemia. Int J Hyperthermia 18;506-520, 2002 https://doi.org/10.1080/02656730110116696