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Related Experiment Videos

Signal 3 availability limits the CD8 T cell response to a solid tumor.

Julie M Curtsinger1, Michael Y Gerner, Debra C Lins

  • 1Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|May 22, 2007
PubMed
Summary
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Cytokine IL-12 acts as a crucial third signal for CD8 T cell survival and function. Supplementing IL-12 in tumor models enhances T cell response and controls tumor growth, demonstrating its therapeutic potential.

Area of Science:

  • Immunology
  • Cancer Biology
  • T cell immunology

Background:

  • CD8 T cells require antigen (Ag), costimulation, and a third signal (signal 3) for optimal effector function.
  • Signal 3 can be provided by cytokines like Interleukin-12 (IL-12) or type I Interferon (IFN).
  • Tumor microenvironments can be deficient in essential signal 3 cytokines, impairing anti-tumor T cell responses.

Purpose of the Study:

  • To investigate the role of signal 3 cytokines in supporting CD8 T cell responses against tumors.
  • To determine if IL-12 administration can enhance adoptively transferred T cells to control tumor growth.
  • To elucidate the mechanism by which IL-12 exerts its therapeutic effect on tumor-specific CD8 T cells.

Main Methods:

  • Adoptive transfer of OVA-specific OT-I T cells into mice bearing E.G7 tumors.

Related Experiment Videos

  • Utilizing OT-I T cells with intact or deficient IL-12 and type I IFN receptors.
  • Administering IL-12 at a later stage of tumor progression.
  • Assessing T cell expansion, effector function (granzyme B, IFN-gamma), tumor infiltration, and tumor growth control.

    • Main Results:

    • Adoptively transferred OT-I T cells in tumor-bearing mice showed limited expansion and effector function, failing to control tumor growth.
    • OT-I T cells lacking IL-12 and type I IFN receptors exhibited transient expansion and rapid disappearance.
    • IL-12 administration significantly enhanced expansion and effector functions of wild-type OT-I cells, leading to tumor growth control.
    • The therapeutic effect of IL-12 was dependent on the presence of its receptor on CD8 T cells, indicating a direct action.

    Conclusions:

    • Tumor-bearing hosts often provide insufficient signal 3 cytokines for optimal CD8 T cell anti-tumor immunity.
    • IL-12 administration can overcome signal 3 deficiency, promoting robust CD8 T cell expansion and effector function.
    • IL-12 therapy directly benefits tumor-specific CD8 T cells, enabling effective tumor control in a deficient microenvironment.