Human glioma immunobiology in vitro: Implications for immunogene therapy

OBJECTIVE: Human gliomas are known to be immunosuppressive. Recent reports have suggested novel strategies to overcome this immunosuppression, includi ng immunogene therapy. We examined expression of 10 immunologically importa nt molecules by human gliomas in vitro, and we discuss the implications for immunogene therapy. METHODS: Early passage human glioma cultures and established human glioma c ell lines were analyzed by now cytometry for expression of Class I and II m ajor histocompatibility complex (MHC), B7-2 (CD86), and Fas (CD95). Culture supernatants were assayed by enzyme-linked immunosorbent assay for interle ukin (IL)-6, IL-10, IL-12, transforming growth factor beta 2, prostaglandin E2, and granulocyte-macrophage colony-stimulating factor levels. RESULTS: All cultures (16 of 16 samples) expressed Class I MHC and Fas, but few expressed Class II MHC (1 of 16 samples) or B7-2 (0 of 16 samples). Ne arly all expressed high levels of IL-6 (19 of 21 samples; mean, 36.5 +/- 10 .8 ng/10(6) cells/d) and prostaglandin E2 (21 of 21 samples; mean, 15.6 +/- 4.5 ng/10(6) cells/d) levels, and many expressed transforming growth facto r beta 2 (13 of 21 samples; mean, 8.6 +/- 3.7 ng/10(6) cells/d). Although s everal cultures (6 of 14 samples) expressed granulocyte-macrophage colony-s timulating factor, expression levels were very low (mean, 0.2 +/- 0.1 ng/10 (6) cells/d). Few cultures (4 of 21 samples) expressed measurable IL-10, an d none (0 of 22 samples) expressed IL-12. CONCLUSION: Class I MHC and Fas expression suggests that human glioma cells may be susceptible to Class I MHC-dependent cytotoxic T cell recognition a nd Fas-mediated killing. Unfortunately, transforming growth factor beta 2 a nd prostaglandin E2 probably impair T cell activation, and IL-6 may shift i mmunity to less effective humoral (T helper 2) responses. Proinflammatory g ene expression (B7-2, granulocyte-macrophage colony-stimulating factor, and /or IL-12) is lacking. Together, these results suggest that modifying gliom a cells via proinflammatory gene transfer or immunoinhibitory gene suppress ion might stimulate immune responses that are effective against unmodified tumors.