Granulocyte/macrophage colony-stimulating factor and interleukin-4-induced dendritic cells.

BACKGROUND We investigated whether GM-CSF/IL-4 is the most efficient cytokine combination for differentiating dendritic cells (DC) in terms of its ability to elicit an antitumor immune response. MATERIALS AND METHODS Two experimental models were examined: C57BL/6 mice bearing MC38 cells and Balb/c mice bearing cachexia-inducible Colon-26 cells. After immunization with DC pulsed with whole tumor cell lysate, tumors were inoculated into the subcutis. RESULTS C57BL/6 mice immunized with lysate-pulsed DC effectively rejected the MC38 challenge and detectable MC38-specific cytotoxic lymphocytes (CTL) were observed. However, even those groups immunized with lysate-pulsed DC exhibited no protective immunity against Colon-26 challenge in Balb/c mice. Unexpectedly, mice inoculated with lysate-unpulsed DC showed an acceleration of cachectic progression (p=0.031) compared to control mice. CONCLUSION We speculate that GM-CSF/IL-4-induced DC promotes Th2-dominated immunity in Balb/c mice. Consideration might be given to which combination of cytokines is appropriate for the ex vivo differentiation of DC in tumor immunotherapy.

[1]  M. Miyata,et al.  Splenectomy before tumor inoculation prolongs the survival time of cachectic mice , 1995, Cancer Immunology, Immunotherapy.

[2]  K. Lundholm,et al.  Experimental cancer cachexia: the role of host-derived cytokines interleukin (IL)-6, IL-12, interferon-gamma, and tumor necrosis factor alpha evaluated in gene knockout, tumor-bearing mice on C57 Bl background and eicosanoid-dependent cachexia. , 2000, Cancer research.

[3]  A. Ohta,et al.  The critical role of Th1-dominant immunity in tumor immunology , 2000, Cancer Chemotherapy and Pharmacology.

[4]  A. Ohta,et al.  Functional heterogeneity among bone marrow-derived dendritic cells conditioned by T(h)1- and T(h)2-biasing cytokines for the generation of allogeneic cytotoxic T lymphocytes. , 2000, International immunology.

[5]  Y. Tokura,et al.  Downregulation of innate and acquired antitumor immunity by bystander gammadelta and alphabeta T lymphocytes with Th2 or Tr1 cytokine profiles. , 1999, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[6]  T. Nishimura,et al.  Functional skewing of bone marrow-derived dendritic cells by Th1- or Th2-inducing cytokines. , 1999, Immunology letters.

[7]  K. Bottomly.  T Cells and Dendritic Cells Get Intimate , 1999, Science.

[8]  H. O’Neill,et al.  Dendritic Cell Immunotherapy for Melanoma , 1999 .

[9]  R. Maldonado-López,et al.  CD8α+ and CD8α− Subclasses of Dendritic Cells Direct the Development of Distinct T Helper Cells In Vivo , 1999, The Journal of experimental medicine.

[10]  T. Luger,et al.  Generation of tumor immunity by bone marrow-derived dendritic cells correlates with dendritic cell maturation stage. , 1999, Journal of immunology.

[11]  H. O’Neill,et al.  Review: dendritic cell immunotherapy for melanoma. , 1999, Cancer biotherapy & radiopharmaceuticals.

[12]  J. Mulé,et al.  Comparative Analysis of Murine Dendritic Cells Derived from Spleen and Bone Marrow , 1998, Journal of immunotherapy.

[13]  J. Mulé,et al.  Murine dendritic cells pulsed with whole tumor lysates mediate potent antitumor immune responses in vitro and in vivo. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[14]  H. Seigler,et al.  Vaccination with dendritic cells inhibits the growth of hepatic metastases in B6 mice. , 1998, Cellular immunology.

[15]  E. Gilboa,et al.  Immunotherapy of cancer with dendritic-cell-based vaccines , 1998, Cancer Immunology, Immunotherapy.

[16]  A. Ohta,et al.  Manipulation of Th1/Th2 balance in vivo by adoptive transfer of antigen-specific Th1 or Th2 cells. , 1997, Journal of immunological methods.

[17]  W. Heath,et al.  Induction of a CD8+ Cytotoxic T Lymphocyte Response by Cross-priming Requires Cognate CD4+ T Cell Help , 1997, The Journal of experimental medicine.

[18]  A. Ohta,et al.  Involvement of IL-4-producing Vbeta8.2+ CD4+ CD62L- CD45RB- T cells in non-MHC gene-controlled predisposition toward skewing into T helper type-2 immunity in BALB/c mice. , 1997, Journal of immunology.

[19]  L. Zitvogel,et al.  Bone Marrow‐Derived Dendritic Cells Serve as Potent Adjuvants for Peptide‐Based Antitumor Vaccines , 1997, Stem cells.

[20]  E. Fikrig,et al.  Interleukin (IL)-6 Directs the Differentiation of IL-4–producing CD4+ T Cells , 1997, The Journal of experimental medicine.

[21]  H. Ishitsuka,et al.  Murine interleukin‐12 prevents the development of cancer cachexia in a murine model , 1996, International journal of cancer.

[22]  K. Mechtler,et al.  Transloading of tumor cells with foreign major histocompatibility complex class I peptide ligand: a novel general strategy for the generation of potent cancer vaccines. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[23]  E. Gilboa,et al.  Induction of antitumor immunity using bone marrow-generated dendritic cells. , 1996, Journal of immunology.

[24]  H. Maeda,et al.  TGF-beta contributes to the shift toward Th2-type responses through direct and IL-10-mediated pathways in tumor-bearing mice. , 1996, Journal of immunology.

[25]  D. Longo,et al.  Gradual loss of T-helper 1 populations in spleen of mice during progressive tumor growth. , 1995, Journal of the National Cancer Institute.

[26]  M. Miyata,et al.  Manifestations of cancer cachexia induced by colon 26 adenocarcinoma are not fully ascribable to interleukin‐6 , 1995, International journal of cancer.

[27]  H. Ishitsuka,et al.  Establishment and characterization of cachexia‐inducing and ‐non‐inducing clones of murine colon 26 carcinoma , 1995, International journal of cancer.

[28]  H. Kimura,et al.  Phenotype and function of dendritic cells derived from rat bone marrow cell cultures. , 1995, Transplantation proceedings.

[29]  W. Paul,et al.  Lymphocyte responses and cytokines , 1994, Cell.

[30]  M. Mehlig,et al.  Dendritic cells from mouse bone marrow: in vitro differentiation using low doses of recombinant granulocyte-macrophage colony-stimulating factor. , 1992, Journal of immunological methods.

[31]  B. Diamond,et al.  Revisiting and revising suppressor T cells. , 1992, Immunology today.

[32]  S. Kaufmann,et al.  The role of T-cell subsets and cytokines in the regulation of infection. , 1991, Immunology today.

[33]  R. Steinman,et al.  The dendritic cell system and its role in immunogenicity. , 1991, Annual review of immunology.

[34]  R. Puri,et al.  In vitro and in vivo antitumor properties of a T-cell clone generated from murine tumor-infiltrating lymphocytes. , 1990, Journal of biological response modifiers.

[35]  T. Decker,et al.  A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. , 1988, Journal of immunological methods.

[36]  T. Takami,et al.  Lymphoid cell subpopulations infiltrating into autologous rat tumors undergoing rejection. , 1984, Cancer research.

[37]  F. Schabel,et al.  Tumor induction relationships in development of transplantable cancers of the colon in mice for chemotherapy assays, with a note on carcinogen structure. , 1975, Cancer research.