Human glioma-induced immunosuppression involves soluble factor(s) that alters monocyte cytokine profile and surface markers

Jian Ping Zou, Lorri A. Morford, Claire Chougnet, Amy R. Dix, Andrew G. Brooks, Naomi Torres, Jon D. Shuman, John E. Coligan, William H. Brooks, Thomas L. Roszman, Gene M. Shearer

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

Abstract

Patients with gliomas exhibit deficient in vitro and in vivo T cell immune activity, and human glioblastoma culture supernatants (GCS) inhibit in vitro T lymphocyte responses. Because APC are essential for initiating and regulating T cell responses, we investigated whether GCS would affect cytokines produced by monocytes and T cells from healthy donors of PBMC. Incubation of PBMC with GCS decreased production of IL-12, IFN-γ, and TNF- α, and increased production of IL-6 and IL-10. The GCS-induced changes in IL-12 and IL-10 occurred in monocytes, and involved changes in IL-12 p40 and IL-10 mRNA expression. Incubation with GCS also resulted in reduced expression of MHC class II and of CD80/86 costimulatory molecules on monocytes. The immunosuppressive effects were not the result of IL-6 or TGF- β1 that was detected in GCS. However, it was due to a factor(s) that is resistant to pH extremes, differentially susceptible to temperature, susceptible to trypsin, and has a minimum molecular mass of 40 kDa. Our findings show that glioblastoma-generated factors that are known to suppress T cell responses alter the cytokine profiles of monocytic APC that, in turn, inhibit T cell function. This model indicates that monocytes can serve as an intermediate between tumor-generated immune-suppressive factors and the T cell responses that are suppressed in gliomas.

Original languageEnglish
Pages (from-to)4882-4892
Number of pages11
JournalJournal of Immunology
Volume162
Issue number8
StatePublished - Apr 15 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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