Immunogenicity of Premalignant Lesions is the Primary Cause of General Cytotoxic T Lymphocyte Unresponsiveness

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2008 Jun 25

PMID 18573907

Citations 51

Authors

Gerald Willimsky

Melinda Czeh

Christoph Loddenkemper

Johanna Gellermann

Karin Schmidt

Peter Wust

Harald Stein

Thomas Blankenstein

Affiliations

Soon will be listed here.

Abstract

Cancer is sporadic in nature, characterized by an initial clonal oncogenic event and usually a long latency. When and how it subverts the immune system is unknown. We show, in a model of sporadic immunogenic cancer, that tumor-specific tolerance closely coincides with the first tumor antigen recognition by B cells. During the subsequent latency period until tumors progress, the mice acquire general cytotoxic T lymphocyte (CTL) unresponsiveness, which is associated with high transforming growth factor (TGF) beta1 levels and expansion of immature myeloid cells (iMCs). In mice with large nonimmunogenic tumors, iMCs expand but TGF-beta1 serum levels are normal, and unrelated CTL responses are undiminished. We conclude that (a) tolerance to the tumor antigen occurs at the premalignant stage, (b) tumor latency is unlikely caused by CTL control, and (c) a persistent immunogenic tumor antigen causes general CTL unresponsiveness but tumor burden and iMCs per se do not.

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