Human Glioma-Induced Immunosuppression Involves Soluble Factor(s) That Alters Monocyte Cytokine Profile and Surface Markers

• Published in: The Journal of immunology (1950) Vol. 162; no. 8; pp. 4882 - 4892
• Main Authors: Zou, Jian-Ping, Morford, Lorri A, Chougnet, Claire, Dix, Amy R, Brooks, Andrew G, Torres, Naomi, Shuman, Jon D, Coligan, John E, Brooks, William H, Roszman, Thomas L, Shearer, Gene M
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.04.1999
• Subjects: Antibodies, Monoclonal - pharmacology; Antigens, CD - biosynthesis; Antigens, CD - immunology; Antigens, Surface - biosynthesis; B7-1 Antigen - biosynthesis; B7-1 Antigen - immunology; B7-2 Antigen; Cell-Free System - chemistry; Cell-Free System - immunology; Cytokines - antagonists & inhibitors; Cytokines - biosynthesis; Glioblastoma; Glioma - chemistry; Glioma - immunology; Glioma - metabolism; Histocompatibility Antigens Class I - biosynthesis; Histocompatibility Antigens Class I - immunology; Humans; Interferon-gamma - pharmacology; Interleukin-10 - antagonists & inhibitors; Interleukin-10 - biosynthesis; Interleukin-10 - genetics; Interleukin-10 - immunology; Interleukin-12 - antagonists & inhibitors; Interleukin-12 - biosynthesis; Interleukin-12 - genetics; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Lymphocyte Activation - immunology; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - immunology; Monocytes - immunology; Monocytes - metabolism; Receptors, Interleukin - immunology; Receptors, Interleukin-10; Recombinant Proteins; RNA, Messenger - biosynthesis; Staphylococcus aureus - immunology; Suppressor Factors, Immunologic - chemistry; Suppressor Factors, Immunologic - physiology; T-Lymphocytes - immunology; Tumor Cells, Cultured
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.162.8.4882

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-gamma, and TNF-alpha, 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-beta1 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.