Annals of Surgical Oncology

, Volume 3, Issue 4, pp 381–386 | Cite as

In vivo effects of locally secreted IL-10 on the murine antitumor immune response

  • Richard J. BarthJr
  • Michael A. Coppola
  • William R. Green
Original Articles
Received:
Accepted:

Abstract

Background: Interleukin-10 (IL-10) is a cytokine secreted by the TH2 class of murine lymphocytes that suppresses the secretion of interferon-γ (IFN-γ) by TH1 lymphocytes and inhibits macrophage-mediated T-cell stimulation and cytotoxicity. The observation that IL-10 is produced by human carcinomas in vitro and in vivo led to the hypothesis that this cytokine plays a role in the suppression of the human anti-tumor immune response. We tested this hypothesis in a murine model.

Methods: To evaluate the effect of IL-10 on the induction of an anti-tumor immune response, mice were immunized with tumor cells transfected with the IL-10 gene and then challenged with parental tumor. The effect of the local secretion of IL-10 on an established immune response was tested by immunizing mice with parental tumor and then challenging with IL-10-secreting tumors.

Results: IL-10-secreting tumors were as effective immunogens as control tumors. Immune mice rejected IL-10-secreting tumors as readily as control challenge tumors. In an in vitro assay, IL-10 did not inhibit CD8 lymphocyte secretion of IFN-γ in response to tumor stimulation. One IL-10-secreting tumor clone regressed when injected into naive mice and induced an antigen-specific immune response capable of protecting mice from subsequent tumor challenge.

Conclusions: The local secretion of IL-10 did not inhibit either the induction of an anti-tumor immune response or the ability of established effector cells to reject challenge tumors. In contrast to its effect on TH1 lymphocytes, IL-10 does not inhibit IFN-γ secretion by CD8 lymphocytes.

Key Words

IL-10 Immunosuppression CD8+ lymphocyte Tumor transfection Vaccine 
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Copyright information

© The Society of Surgical Oncology, Inc. 1996

Authors and Affiliations

  • Richard J. BarthJr
    • 1
  • Michael A. Coppola
    • 2
  • William R. Green
    • 2
  1. 1.From the Department of SurgeryDartmouth Medical School and Norris Cotton Cancer CenterLebanonUSA
  2. 2.the Department of MicrobiologyDartmouth Medical School and Norris Cotton Cancer CenterLebanonUSA

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