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

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