Tumor regression after adoptive transfer of effector T cells is independent of perforin or Fas ligand (APO-1L/CD95L).
作者： Walter J. Urba , Hong-Ming Hu , Bernard A. Fox , Hauke Winter
DOI:
关键词: Melanoma 、 Perforin 、 Cancer research 、 Adoptive cell transfer 、 Biology 、 Fas ligand 、 Immunity 、 Effector 、 Wild type 、 Cytotoxicity 、 Immunology
摘要: The adoptive transfer of tumor-specific effector T cells can result in complete regression and cure mice with systemic melanoma, but the mechanisms responsible for are not well characterized. Perforin- Fas ligand (APO-1/CD95 ligand)-mediated cytotoxicity have been proposed as cell-mediated tumor destruction. To determine role perforin (FasL) a murine melanoma model, B16BL6-D5 (D5), we generated D5-specific from vaccine-draining lymph nodes wild type (wt), knock out (PKO), or FasL mutant (gld) treated established D5 metastases same genotype. Effector wt, PKO gld induced pulmonary significantly prolonged survival animals regardless their Complete by was also observed sarcoma model (MCA-310). Furthermore, wt provided long-term immunity to D5. Therapeutic PKO, exhibit 1 cytokine profile; they secrete IFN-gamma, IL-4. In these models, antitumor independent.
jimmunol.org 参考文章(68)
Robert A. Krinock, Jeffrey J. Sussman, Alfred E. Chang, Suyu Shu, Takafumi Matsumura, David S. Terman, Bernard A. Fox, Stimulation of tumor-draining lymph node cells with superantigenic staphylococcal toxins leads to the generation of tumor-specific effector T cells. Journal of Immunology. ,vol. 152, pp. 1277- 1288 ,(1994)
Joseph D. Feldman, Eduardo Fernandez-Cruz, Barbara Halliburton, In vivo elimination by specific effector cells of an established syngeneic rat moloney virus-induced sarcoma. Journal of Immunology. ,vol. 123, pp. 1772- 1777 ,(1979)
Francis V. Chisari, Valerie Pasquetto, Luca G. Guidotti, Yasunari Nakamoto, Robert D. Schreiber, Differential target cell sensitivity to CTL-activated death pathways in hepatitis B virus transgenic mice. Journal of Immunology. ,vol. 158, pp. 5692- 5697 ,(1997)
Reinhold Schirmbeck, Jörg Reimann, Stefan Thoma, Frank Leithäuser, Waltraud Böhm, Peter Möller, T cell-mediated, IFN-gamma-facilitated rejection of murine B16 melanomas. Journal of Immunology. ,vol. 161, pp. 897- 908 ,(1998)
Noriaki Sadanaga, Ulrike L. Burger, Maximilian P. Chang, Timothy J. Eberlein, Peter S. Goedegebuure, Makoto Nagoshi, Successful adoptive cellular immunotherapy is dependent on induction of a host immune response triggered by cytokine (IFN-gamma and granulocyte/macrophage colony-stimulating factor) producing donor tumor-infiltrating lymphocytes. Journal of Immunology. ,vol. 160, pp. 334- 344 ,(1998)
P D Greenberg, Therapy of murine leukemia with cyclophosphamide and immune Lyt-2+ cells: cytolytic T cells can mediate eradication of disseminated leukemia. Journal of Immunology. ,vol. 136, pp. 1917- 1922 ,(1986)
Suyu Shu, Hirohisa Yoshizawa, Alfred E. Chang, Cellular interactions in effector cell generation and tumor regression mediated by anti-CD3/interleukin 2-activated tumor-draining lymph node cells. Cancer Research. ,vol. 52, pp. 1129- 1136 ,(1992)
Paula H. Chauvenet, Carole P. McArthur, Richard T. Smith, Demonstration in vitro of Cytotoxic T Cells with Apparent Specificity Toward Tumor-Specific Transplantation Antigens on Chemically Induced Tumors Journal of Immunology. ,vol. 123, pp. 2575- 2581 ,(1979)
Laura L. Carter, Richard W. Dutton, Relative perforin- and Fas-mediated lysis in T1 and T2 CD8 effector populations. Journal of Immunology. ,vol. 155, pp. 1028- 1031 ,(1995)
Walter J. Urba, Hong-Ming Hu, Bernard A. Fox, Gene-Modified Tumor Vaccine with Therapeutic Potential Shifts Tumor-Specific T Cell Response from a Type 2 to a Type 1 Cytokine Profile Journal of Immunology. ,vol. 161, pp. 3033- 3041 ,(1998)