Search tips
Search criteria 


Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Exp Med. 1996 January 1; 183(1): 283–287.
PMCID: PMC2192396

Peptide-pulsed dendritic cells induce antigen-specific CTL-mediated protective tumor immunity


Cytotoxic T lymphocytes (CTLs) are a critical component of the immune response to tumors. Tumor-derived peptide antigens targeted by CTLs are being defined for several human tumors and are potential immunogens for the induction of specific antitumor immunity. Dendritic cells (DC) are potent antigen-presenting cells (APCs) capable of priming CTL responses in vivo. Here we show that major histocompatibility complex class I- presented peptide antigen pulsed onto dendritic APCs induces protective immunity to lethal challenge by a tumor transfected with the antigen gene. The immunity is antigen specific, requiring expression of the antigen gene by the tumor target, and is eliminated by in vivo depletion of CD8+ T cells. Furthermore, mice that have rejected the transfected tumor are protected from subsequent challenge with the untransfected parent tumor. These results suggest that immunization strategies using antigen-pulsed DC may be useful for inducing tumor- specific immune responses.

Full Text

The Full Text of this article is available as a PDF (499K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Doherty PC, Knowles BB, Wettstein PJ. Immunological surveillance of tumors in the context of major histocompatibility complex restriction of T cell function. Adv Cancer Res. 1984;42:1–65. [PubMed]
  • Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, Toy ST, Simon P, Lotze MT, Yang JC, Seipp CA, et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med. 1988 Dec 22;319(25):1676–1680. [PubMed]
  • Aebersold P, Hyatt C, Johnson S, Hines K, Korcak L, Sanders M, Lotze M, Topalian S, Yang J, Rosenberg SA. Lysis of autologous melanoma cells by tumor-infiltrating lymphocytes: association with clinical response. J Natl Cancer Inst. 1991 Jul 3;83(13):932–937. [PubMed]
  • Yewdell JW, Bennink JR. Cell biology of antigen processing and presentation to major histocompatibility complex class I molecule-restricted T lymphocytes. Adv Immunol. 1992;52:1–123. [PubMed]
  • Townsend A, Trowsdale J. The transporters associated with antigen presentation. Semin Cell Biol. 1993 Feb;4(1):53–61. [PubMed]
  • Slingluff CL, Jr, Hunt DF, Engelhard VH. Direct analysis of tumor-associated peptide antigens. Curr Opin Immunol. 1994 Oct;6(5):733–740. [PubMed]
  • Pardoll DM. Tumour antigens. A new look for the 1990s. Nature. 1994 Jun 2;369(6479):357–357. [PubMed]
  • Boon T. Toward a genetic analysis of tumor rejection antigens. Adv Cancer Res. 1992;58:177–210. [PubMed]
  • Inaba K, Metlay JP, Crowley MT, Witmer-Pack M, Steinman RM. Dendritic cells as antigen presenting cells in vivo. Int Rev Immunol. 1990;6(2-3):197–206. [PubMed]
  • Steinman RM, Witmer-Pack M, Inaba K. Dendritic cells: antigen presentation, accessory function and clinical relevance. Adv Exp Med Biol. 1993;329:1–9. [PubMed]
  • Inaba K, Romani N, Steinman RM. An antigen-independent contact mechanism as an early step in T cell-proliferative responses to dendritic cells. J Exp Med. 1989 Aug 1;170(2):527–542. [PMC free article] [PubMed]
  • Chen L, Linsley PS, Hellström KE. Costimulation of T cells for tumor immunity. Immunol Today. 1993 Oct;14(10):483–486. [PubMed]
  • Sallusto F, Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med. 1994 Apr 1;179(4):1109–1118. [PMC free article] [PubMed]
  • Romani N, Gruner S, Brang D, Kämpgen E, Lenz A, Trockenbacher B, Konwalinka G, Fritsch PO, Steinman RM, Schuler G. Proliferating dendritic cell progenitors in human blood. J Exp Med. 1994 Jul 1;180(1):83–93. [PMC free article] [PubMed]
  • Inaba K, Steinman RM, Pack MW, Aya H, Inaba M, Sudo T, Wolpe S, Schuler G. Identification of proliferating dendritic cell precursors in mouse blood. J Exp Med. 1992 May 1;175(5):1157–1167. [PMC free article] [PubMed]
  • Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S, Muramatsu S, Steinman RM. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med. 1992 Dec 1;176(6):1693–1702. [PMC free article] [PubMed]
  • Bastin J, Rothbard J, Davey J, Jones I, Townsend A. Use of synthetic peptides of influenza nucleoprotein to define epitopes recognized by class I-restricted cytotoxic T lymphocytes. J Exp Med. 1987 Jun 1;165(6):1508–1523. [PMC free article] [PubMed]
  • Inaba K, Young JW, Steinman RM. Direct activation of CD8+ cytotoxic T lymphocytes by dendritic cells. J Exp Med. 1987 Jul 1;166(1):182–194. [PMC free article] [PubMed]
  • Macatonia SE, Taylor PM, Knight SC, Askonas BA. Primary stimulation by dendritic cells induces antiviral proliferative and cytotoxic T cell responses in vitro. J Exp Med. 1989 Apr 1;169(4):1255–1264. [PMC free article] [PubMed]
  • Inaba K, Metlay JP, Crowley MT, Steinman RM. Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ. J Exp Med. 1990 Aug 1;172(2):631–640. [PMC free article] [PubMed]
  • Townsend A, Elliott T, Cerundolo V, Foster L, Barber B, Tse A. Assembly of MHC class I molecules analyzed in vitro. Cell. 1990 Jul 27;62(2):285–295. [PubMed]
  • 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. 1995 Jul 1;182(1):255–260. [PMC free article] [PubMed]
  • Moore MW, Carbone FR, Bevan MJ. Introduction of soluble protein into the class I pathway of antigen processing and presentation. Cell. 1988 Sep 9;54(6):777–785. [PubMed]
  • Falo LD, Jr, Kovacsovics-Bankowski M, Thompson K, Rock KL. Targeting antigen into the phagocytic pathway in vivo induces protective tumour immunity. Nat Med. 1995 Jul;1(7):649–653. [PubMed]
  • Falk K, Rötzschke O, Stevanović S, Jung G, Rammensee HG. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature. 1991 May 23;351(6324):290–296. [PubMed]
  • Rock KL, Rothstein L, Gamble S. Generation of class I MHC-restricted T-T hybridomas. J Immunol. 1990 Aug 1;145(3):804–811. [PubMed]
  • Rock KL, Fleischacker C, Gamble S. Peptide-priming of cytolytic T cell immunity in vivo using beta 2-microglobulin as an adjuvant. J Immunol. 1993 Feb 15;150(4):1244–1252. [PubMed]
  • Benjamin RJ, Madrigal JA, Parham P. Peptide binding to empty HLA-B27 molecules of viable human cells. Nature. 1991 May 2;351(6321):74–77. [PubMed]
  • Auchincloss H, Jr, Ghobrial RR, Russell PS, Winn HJ. Prevention of alloantibody formation after skin grafting without prolongation of graft survival by anti-L3T4 in vivo. Transplantation. 1988 Jun;45(6):1118–1123. [PubMed]
  • Grabbe S, Beissert S, Schwarz T, Granstein RD. Dendritic cells as initiators of tumor immune responses: a possible strategy for tumor immunotherapy? Immunol Today. 1995 Mar;16(3):117–121. [PubMed]
  • Tazi A, Bouchonnet F, Grandsaigne M, Boumsell L, Hance AJ, Soler P. Evidence that granulocyte macrophage-colony-stimulating factor regulates the distribution and differentiated state of dendritic cells/Langerhans cells in human lung and lung cancers. J Clin Invest. 1993 Feb;91(2):566–576. [PMC free article] [PubMed]
  • Becker Y. Dendritic cell activity against primary tumors: an overview. In Vivo. 1993 May-Jun;7(3):187–191. [PubMed]
  • Azizi E, Bucana C, Goldberg L, Kripke ML. Perturbation of epidermal Langerhans cells in basal cell carcinomas. Am J Dermatopathol. 1987 Dec;9(6):465–473. [PubMed]
  • Murphy GF, Radu A, Kaminer M, Berd D. Autologous melanoma vaccine induces inflammatory responses in melanoma metastases: relevance to immunologic regression and immunotherapy. J Invest Dermatol. 1993 Mar;100(3):335S–341S. [PubMed]
  • Tsujitani S, Kakeji Y, Watanabe A, Kohnoe S, Maehara Y, Sugimachi K. Infiltration of dendritic cells in relation to tumor invasion and lymph node metastasis in human gastric cancer. Cancer. 1990 Nov 1;66(9):2012–2016. [PubMed]
  • Grabbe S, Bruvers S, Gallo RL, Knisely TL, Nazareno R, Granstein RD. Tumor antigen presentation by murine epidermal cells. J Immunol. 1991 May 15;146(10):3656–3661. [PubMed]
  • Cohen PJ, Cohen PA, Rosenberg SA, Katz SI, Mulé JJ. Murine epidermal Langerhans cells and splenic dendritic cells present tumor-associated antigens to primed T cells. Eur J Immunol. 1994 Feb;24(2):315–319. [PubMed]
  • Flamand V, Sornasse T, Thielemans K, Demanet C, Bakkus M, Bazin H, Tielemans F, Leo O, Urbain J, Moser M. Murine dendritic cells pulsed in vitro with tumor antigen induce tumor resistance in vivo. Eur J Immunol. 1994 Mar;24(3):605–610. [PubMed]
  • Zou JP, Shimizu J, Ikegame K, Yamamoto N, Ono S, Fujiwara H, Hamaoka T. Tumor-bearing mice exhibit a progressive increase in tumor antigen-presenting cell function and a reciprocal decrease in tumor antigen-responsive CD4+ T cell activity. J Immunol. 1992 Jan 15;148(2):648–655. [PubMed]
  • Shimizu J, Suda T, Yoshioka T, Kosugi A, Fujiwara H, Hamaoka T. Induction of tumor-specific in vivo protective immunity by immunization with tumor antigen-pulsed antigen-presenting cells. J Immunol. 1989 Feb 1;142(3):1053–1059. [PubMed]
  • Falo LD, Jr, Colarusso LJ, Benacerraf B, Rock KL. Serum proteases alter the antigenicity of peptides presented by class I major histocompatibility complex molecules. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8347–8350. [PubMed]
  • Mayordomo JI, Zorina T, Storkus WJ, Zitvogel L, Celluzzi C, Falo LD, Melief CJ, Ildstad ST, Kast WM, Deleo AB, et al. Bone marrow-derived dendritic cells pulsed with synthetic tumour peptides elicit protective and therapeutic antitumour immunity. Nat Med. 1995 Dec;1(12):1297–1302. [PubMed]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press