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[Cancer Research 59, 911-917, February 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 911-917, February 15, 1999]
© 1999 American Association for Cancer Research

Immunology

Tumor-induced Interleukin-10 Inhibits Type 1 Immune Responses Directed at a Tumor Antigen As Well As a Non-Tumor Antigen Present at the Tumor Site1

Brian K. Halak, Henry C. Maguire, Jr. and Edmund C. Lattime2

Immunology Program, Kimmel Cancer Center [B. K. H., E. C. L.] and Department of Medicine [H. C. M., E. C. L.], Division of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107; and Department of Surgery, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School and The Cancer Institute of New Jersey, New Brunswick, NJ 08901 [E. C. L.]

Interleukin (IL)-10 is a potent immunosuppressive cytokine that has been found to be present at the tumor site in a wide variety of human cancers, including transitional cell carcinoma of the bladder. Using a murine bladder tumor (MB49), which we show to express the male transplantation antigen (HY), we tested the hypothesis that IL-10 at the tumor site can block the generation of a tumor-specific type 1 immune response. We show that, despite its expression of HY, MB49 fails to prime for an HY-specific type 1 (IFN-{gamma}) response in normal female mice. Although MB49 does not constitutively produce IL-10, our data support a model whereby MB49 induces infiltrating cells to produce IL-10. This feature rendered the IL-10 knockout (KO) mouse, whose infiltrating cells are incapable of IL-10 production, a suitable model in which to study MB49 in the absence of IL-10. When injected into IL-10 KO mice, MB49 does prime for an HY-specific, type 1 immune response. Furthermore, IL-10 KO mice show prolonged survival and an increased capacity to reject tumors as compared with normal mice. We also tested the ability of tumor-induced IL-10 to inhibit immunization to a non-tumor antigen present at the tumor site. When vaccinia virus encoding ß-galactosidase (ß-gal) is injected into the tumors of normal mice, no ß-gal-specific IFN-{gamma} response is mounted. However, when this same viral construct is injected into the tumors of IL-10 KO mice, it produces a strong ß-gal-specific, IFN-{gamma} response. These studies demonstrate that tumor-induced IL-10 can block the generation of a tumor-specific type 1 immune response as well as subvert attempts to elicit a type 1 immune response to a non-tumor antigen at the tumor site.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.