HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Stewart, T. J. Articles by Abrams, S. I. Search for Related Content PubMed PubMed Citation Articles by Stewart, T. J. Articles by Abrams, S. I.

Altered Immune Function during Long-Term Host-Tumor Interactions Can Be Modulated to Retard Autochthonous Neoplastic Growth¹

Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892

Ag-specific and generalized forms of immunosuppression have been documented in animal tumor models. However, much of our knowledge on tumor-induced immunosuppression was acquired using tumor implant models, which do not reiterate the protracted nature of host-tumor interactions. Therefore, a transgenic mouse model of autochthonous mammary tumor development and progression was chosen to investigate the long-term consequences of neoplastic growth on the immune system. In vitro proliferation of unfractionated splenocytes from tumor-bearing mice, as assessed by [³H]thymidine uptake, was inhibited by the presence of suppressor cells within these splenocyte preparations, because purifying the T cells restored their biological activity. However, the level of inhibition did not correlate with either tumor load or the percentage of myeloid-derived CD11b⁺Gr1⁺ cells. To evaluate tumor-specific immune dysfunction, transgenic mice were challenged with autologous tumor cells. Mice with extensive, but not minimal autochthonous tumor burdens demonstrated a significantly enhanced rate of autologous tumor growth compared with age-matched controls. In contrast, an allogeneic tumor challenge was efficiently rejected from both groups of transgenic mice. It was also noted that allogeneic tumor challenge of mice with minimal disease significantly inhibited autochthonous primary tumor growth. We therefore demonstrated that 1) a generalized form of immunosuppression occurred, but not as a result of permanent alterations to T cell function, because purified T cell subsets retained normal biological activity following polyclonal or allostimulation; and 2) tumor-specific immunosuppression emerged as a consequence of tumor progression, but could be modulated to enhance antitumor responses against autochthonous primary neoplastic growth.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research.

² Address correspondence and reprint requests to Dr. Scott I. Abrams, Laboratory of Tumor Immunology and Biology, National Cancer Institute, 10 Center Drive, Building 10-5B46, Bethesda, MD 20892. E-mail address: sa47z{at}nih.gov

³ Abbreviations used in this paper: Tg, transgene; DC, dendritic cell; LNC, lymph node cell; MDSC, myeloid-derived suppressor cell; LN, lymph node.