Tumor lysate-pulsed dendritic cells can elicit an effective antitumor immune response during early lymphoid recovery

被引:141
作者
Asavaroengchai, W
Kotera, Y
Mulé, JJ
机构
[1] Univ Michigan, Med Ctr, Dept Surg, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Med Ctr, Dept Pathol, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA
关键词
D O I
10.1073/pnas.022634999
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Dendritic cells (DC) can serve to immunize the newborn immune system to foreign antigen. In a lymphopenic environment, naive T cells undergoing homeostasis-driven proliferation can acquire increased sensitivity to antigen stimulation. Here, we evaluated the capacity of DC to effectively prime the host immune system to elicit antitumor effects in the setting of early lymphoid reconstitution after bone marrow transplantation (BMT). Indeed, bone marrow-derived, cytokine-driven DC pulsed with whole tumor lysates (TP-DC) could, early on, prime a specific and long-lasting antitumor immune response, which mediated the rejection of a lethal challenge of a weakly immunogenic breast tumor. In the therapeutic setting, TP-DC could also inhibit the growth of preexisting breast tumor metastases by repetitive immunizations initiated early after BMT. Spleen T cells obtained from mice immunized with TP-DC early after BMT showed a substantial increase in tumor-specific IFN-gamma production. Our findings demonstrate that it is possible to promote effective antitumor immunity in a defined lymphopenic environment through DC-based immunization.
引用
收藏
页码:931 / 936
页数:6
相关论文
共 29 条
  • [11] Grzegorzewski KJ, 1996, BLOOD, V88, P4139
  • [12] GENERATION OF LARGE NUMBERS OF DENDRITIC CELLS FROM MOUSE BONE-MARROW CULTURES SUPPLEMENTED WITH GRANULOCYTE MACROPHAGE COLONY-STIMULATING FACTOR
    INABA, K
    INABA, M
    ROMANI, N
    AYA, H
    DEGUCHI, M
    IKEHARA, S
    MURAMATSU, S
    STEINMAN, RM
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 176 (06) : 1693 - 1702
  • [13] Mackall CL, 1996, J IMMUNOL, V156, P4609
  • [14] DOES T-CELL TOLERANCE REQUIRE A DEDICATED ANTIGEN-PRESENTING CELL
    MATZINGER, P
    GUERDER, S
    [J]. NATURE, 1989, 338 (6210) : 74 - 76
  • [15] Preferential induction of Th1 responses by functionally mature hepatic (CD8α- and CD8α+) dendritic cells -: Association with conversion from liver transplant tolerance to acute rejection
    Morelli, AE
    O'Connell, PJ
    Khanna, A
    Logar, AJ
    Lu, L
    Thomson, AW
    [J]. TRANSPLANTATION, 2000, 69 (12) : 2647 - 2657
  • [16] Cutting edge:: Intravenous soluble antigen is presented to CD4 T cells by CD8- dendritic cells, but cross-presented to CD8 T cells by CD8+ dendritic cells
    Pooley, JL
    Heath, WR
    Shortman, K
    [J]. JOURNAL OF IMMUNOLOGY, 2001, 166 (09) : 5327 - 5330
  • [17] Porgador A, 1996, J IMMUNOL, V156, P2918
  • [18] IDENTIFICATION OF HUMAN CANCERS DEFICIENT IN ANTIGEN PROCESSING
    RESTIFO, NP
    ESQUIVEL, F
    KAWAKAMI, Y
    YEWDELL, JW
    MULE, JJ
    ROSENBERG, SA
    BENNINK, JR
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 177 (02) : 265 - 272
  • [19] Neonatal tolerance revisited: Turning on newborn T cells with dendritic cells
    Ridge, JP
    Fuchs, EJ
    Matzinger, P
    [J]. SCIENCE, 1996, 271 (5256) : 1723 - 1726
  • [20] IFNγ and lymphocytes prevent primary tumour development and shape tumour immunogenicity
    Shankaran, V
    Ikeda, H
    Bruce, AT
    White, JM
    Swanson, PE
    Old, LJ
    Schreiber, RD
    [J]. NATURE, 2001, 410 (6832) : 1107 - 1111