Résumés
Résumé
L’existence de lymphocytes T capables de reconnaître des antigènes spécifiques des tumeurs est maintenant complètement admise. Ces cellules, ainsi que les cellules natural killer (NK), infiltrent le tissu tumoral et sont en mesure d’exercer une cytotoxicité à l’égard des cellules cancéreuses. Cependant, au cours de l’histoire naturelle du développement tumoral, la réponse immunitaire se révèle inefficace. Ce constat est à l’origine de nombreux travaux de recherche dont l’objectif à terme est de concevoir de nouvelles approches thérapeutiques du cancer. L’immunothérapie a fait la preuve de son efficacité sur des modèles expérimentaux de tumeur chez l’animal. La thérapie cellulaire du cancer par cellules immunocompétentes est actuellement en évaluation clinique. Dans ces stratégies thérapeutiques, deux approches sont en évaluation : stimuler in vivo le développement d’une immunité protectrice, à l’aide de cellules présentatrices d’antigènes, ou encore apporter au patient des cellules effectrices éduquées in vitro.
Summary
The identification of tumor specific antigens has provided important advance in tumor immunology. It is now established that specific cytotoxic T lymphocytes (CTL) and natural killer cells infiltrate tumor tissues and are effector cells able to control tumor growth. However, such a natural antitumor immunity has limited effects in cancer patients. Failure of host defenses against tumor is consecutive to several mechanisms which are becoming targets to design new immunotherapeutic approaches. CTL are critical components of the immune response to human tumors and induction of strong CTL responses is the goal of most current vaccine strategies. Effectiveness of cytokine therapy, cancer vaccines and injection of cells improving cellular immunity have been established in tumor grafted murine models. Clinical trials are underway. To day, interest is particularly focused on cell therapy : injected cells are either « ready to use » effector cells (lymphocytes) or antigen presenting cells able to induce a protective immune reaction in vivo (dendritic cells). The challenge ahead lie in the careful optimization of the most promising stategies in clinical situation.
Parties annexes
Références
- 1. Boon T, Brichard VG, Eynde BVD. Antigènes de rejet des tumeurs et immunothérapie spécifique du cancer. Med Sci 1995 ; 11 : 1279-87.
- 2. Eynde BJVD, Gaugler B, Probst-Kepper M, et al. A new antigen recognized by cytolytic T lymphocytes on a human kidney tumor results from reverse strand transcription. J Exp Med 1999 ; 190 : 1793-800.
- 3. Rodriguez A, Regnault A, Kleijmeer M, Ricciardi-Castagnoli P, Amigorena S. Selective transport of internalized antigens to the cytosol for MHC class I presentation in dendritic cells. Nat Cell Biol 1999 ; 1 : 362-8.
- 4. Matzinger P. The danger model : a renewed sense of self. Science 2002 ; 296 : 301-5.
- 5. Imler J, Hoffman J. Toll receptors in innate immunity. Trends Cell Biol 2001 ; 11 : 304-11.
- 6. Delneste Y, Magistrelli G, Gauchat J, et al. Involvement of Lox-1 in dendritic cell mediated antigen cross-presentation. Immunity 2002 ; 17 : 353-62.
- 7. Banchereau J, Schuler-Thurner B, Palucka AK, Schuler G. Dendritic cells as vectors for therapy. Cell 2001 ; 106 : 271-4.
- 8. Barry M, Bleackley RC. Cytotoxic lymphocytes : all roads lead to death. Nat Immunol 2002 ; 2 : 401-9.
- 9. Tjelle TE, Lovdal T, Berg T. Phagosome dybnamics and function. Bioessays 2000 ; 22 : 255-63.
- 10. Grommé M, Uytdehaag FG, Janssen H, et al. Recycling MHC class I molecules and endosomal peptide loading. Proc Natl Acad Sci USA 1999 ; 96 : 10326-31.
- 11. Pittet MJ, Speiser DE, Valmori D, et al. Ex vivo analysis of tumor antigen specific CD8+ T cell responses using MHC/peptide tetramers in cancer patients. Int Immunolpharmacol 2001 ; 1 : 1235-47.
- 12. Bonotte B, Favre N, Moutet M, et al. Bcl2-mediated inhibition of apoptosis prevents immunogenicity and restores tumorigenicity of spontaneously regressive tumors. J Immunol 1998 ; 161 : 1433-8.
- 13. Almand B, Clark JI, Nikitina E, et al. Increased production of immature myeloid cells in cancer patients : a mechanism of immunosuppression in cancer. J Immunol 2001 ; 166 : 678-89.
- 14. Pardoll DM. Cancer vaccines. Nat Med 1998 ; 4 (suppl) : 525-31.
- 15. Sakaguchi S. Regulatory T cells : key controllers of immunologic self-tolerance. Cell 2000 ; 101 : 455-8.
- 16. Chouaib S, Asselin-Paturel C, Mami-Chouaib F, Caignard A, Blay JY. The host-tumor immune conflict : from immunosuppression to resistance and destruction. Immunol Today 1997 ; 18 : 493-7.
- 17. Bodey B, Bodey B Jr, Siegel SE, Kaiser HE. Failure of cancer vaccines : the significant limitations of this approach to immunotherapy. Anticancer Res 2000 ; 20 : 2665-76.
- 18. Negrier S, Escudier B, Lasset C, et al. Recombinant human interleukin-2, recombinant human interferon alpha-2a, or both in metastatic renal-cell carcinoma. N Engl J Med 1998 ; 338 : 1272-8.
- 19. Mulé JJ, Shu S, Schwarz SL, Rosenberg SA. Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin-2. Science 1984 ; 225 : 1487-9.
- 20. Rosenberg S, Spiess P, Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 1986 ; 233 : 1318-21.
- 21. Bouet-Toussaint F, Genetet N, Rioux-Leclercq N, et al. Interleukin 2 expanded lymphocytes from lymph node and tumor biopsies of human renal cell carcinoma, breast and ovarian cancer. Eur Cytokine Netw 2000 ; 11 : 217-24.
- 22. Figlin R, Pierce W, Kaboo R, et al. Treatment of metastatic renal cell carcinoma with nephrectomy, interleukin-2 and cytokine-primed or CD8+ selected tumor infiltrating lymphocytes from primary tumor. J Urol 1997 ; 158 : 740-5.
- 23. Dreno B, Nguyen JM, Khammari A, et al. Randomized trial of adoptive transfer of melanoma tumor-infiltrating lymphocytes as adjuvant therapy for stage III melanoma. Cancer Immunol Immunother 2002 ; 51 : 539-46.
- 24. Biragyn A, Kwak LW. Designer cancer vaccines are still in fashion. Nat Med 2000 ; 6 : 966-8.
- 25. Liau LM, Black KL, Prins RM, et al. Treatment of intracranial gliomas with bone marrow-derived dendritic cells pulsed with tumor antigens. J Neurosurg 1999 ; 90 : 1115-24.
- 26. Zitvogel L, Mayodormo J, Tjandrawan T, et al. Therapy of murine tumors with tumor peptide-pulsed dendritic celles : dependence on T cells, B7 costimulation, and T helper cell-1 associated cytokines. J Exp Med 1996 ; 183 : 87-97.
- 27. Lespagnard L, Mettens P, Verheyden AM, et al. Dendritic cells fused with mastocytoma cells elicit therapeutic antitumor immunity. Int J Cancer 1998 ; 13 : 250-8.
- 28. Wang J, Saffold S, Cao X, Krauss J, Chen W. Eliciting T cell immunity against poorly immunogenic tumors by immunization with dendritic cell-tumor fusion vaccines. J Immunol 1998 ; 161 : 5516-24.
- 29. Murphy G, Tjoa B, Ragde H, et al. Phase I clinical trial : T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen. Prostate 1996 ; 29 : 371-80.
- 30. Nestlé FO, Alijagic S, Gilliet M, et al. 1998. Vaccination of melanoma patients with peptide or tumor lysate-pulsed dendritic cells. Nat Med 1998 ; 4 : 328-32.
- 31. Kugler A, Stuhler G, Walden P, et al. Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids. Nat Med 2000 ; 6 : 332-6.
- 32. Dudley ME, Wunderlich JR, Yang JC, et al. A phase I study of non myeloablative chemotherapy and adoptive transfer of autologous tumor-antigen specific T lymphocytes in patients with metastatic melanoma. J Immunother 2002 ; 25 : 243-51.