In Vivo Effects of Locally Secreted IL-10 on the Murine Antitumor Immune Response

Overview

Journal Ann Surg Oncol

Publisher Springer

Specialty Oncology

Date 1996 Jul 1

PMID 8790851

Citations 3

Authors

R J Barth Jr

M A Coppola

W R Green

Affiliations

Soon will be listed here.

Abstract

Background: Interleukin-10 (IL-10) is a cytokine secreted by the TH2 class of murine lymphocytes that suppresses the secretion of interferon-gamma (IFN-gamma) 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-gamma 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 antitumor 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-gamma secretion by CD8 lymphocytes.

Citing Articles

Interleukin 10 in the tumor microenvironment: a target for anticancer immunotherapy.

Sato T, Mizue Terai , Tamura Y, Alexeev V, Mastrangelo M, Selvan S Immunol Res. 2011; 51(2-3):170-82.

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Reduced tumorigenesis of EG7 after interleukin-10 gene transfer and enhanced efficacy in combination with intratumorally injection of adenovirus-mediated lymphotactin and the underlying mechanism.

Zhang J, Zhou Z, Wang C, Shen J, Zheng Y, Zhang L Cancer Immunol Immunother. 2011; 60(4):559-73.

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Interleukin-10 promotes B16-melanoma growth by inhibition of macrophage functions and induction of tumour and vascular cell proliferation.

Garcia-Hernandez M, Hernandez-Pando R, Gariglio P, Berumen J Immunology. 2002; 105(2):231-43.

PMID: 11872099 PMC: 1782651. DOI: 10.1046/j.1365-2567.2002.01363.x.

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