Enhancement of Antitumor Immunity by CTLA-4 Blockade

@article{Leach1996EnhancementOA,
  title={Enhancement of Antitumor Immunity by CTLA-4 Blockade},
  author={Dana R. Leach and Matthew F. Krummel and James P. Allison},
  journal={Science},
  year={1996},
  volume={271},
  pages={1734 - 1736}
}
One reason for the poor immunogenicity of many tumors may be that they cannot provide signals for CD28-mediated costimulation necessary to fully activate T cells. [] Key Result Here, in vivo administration of antibodies to CTLA-4 resulted in the rejection of tumors, including preestablished tumors. Furthermore, this rejection resulted in immunity to a secondary exposure to tumor cells. These results suggest that blockade of the inhibitory effects of CTLA-4 can allow for, and potentiate, effective immune…
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References

SHOWING 1-10 OF 53 REFERENCES
Manipulation of costimulatory signals to enhance antitumor T-cell responses.
Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4
Tumor rejection after direct costimulation of CD8+ T cells by B7-transfected melanoma cells.
TLDR
Results suggest that B7 expression renders tumor cells capable of effective antigen presentation, leading to their eradication in vivo.
CTLA-4 can function as a negative regulator of T cell activation.
Specificity and longevity of antitumor immune responses induced by B7-transfected tumors.
TLDR
It is found that the immunity induced by K1735 is not restricted to the parental tumor cells but is effective against an additional melanoma line and an unrelated fibrosarcoma as well and irradiation severely diminishes the effectiveness of B7-positive tumor cells as immunogens.
CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation
TLDR
It is shown here that the presence of low levels of B7-2 on freshly explanted T cells can partially inhibit T cell proliferation, and this inhibition is mediated by interactions with CTLA-4, which strongly suggests that the outcome of T cell antigen receptor stimulation is regulated by CD28 costimulatory signals, as well as inhibitory signals derived from CTla-4.
CTLA4 mediates antigen-specific apoptosis of human T cells.
  • J. Gribben, G. Freeman, G. Gray
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1995
TLDR
It is demonstrated that cross-linking of the inducible T-cell surface molecule CTLA4 can mediate apoptosis of previously activated human T lymphocytes, and Regulation of this pathway may provide a novel therapeutic strategy to delete antigen-specific activated T cells.
Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4
TLDR
Although CTLA-4-deficient T cells proliferated spontaneously and strongly when stimulated through the T cell receptor, they were sensitive to cell death induced by cross-linking of the Fas receptor and by gamma irradiation, and is vital for the control of lymphocyte homeostasis.
Constitutive expression of B7 restores immunogenicity of tumor cells expressing truncated major histocompatibility complex class II molecules.
TLDR
The role of B7 activation molecule is illustrated in stimulating potent tumor-specific CD4+ T cells that mediate rejection of wild-type tumors and provides a theoretical basis for immunotherapy of established tumors.
Dendritic cells as initiators of tumor immune responses: a possible strategy for tumor immunotherapy?
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