LPS alters the immuno-phenotype of glioma and glioma stem-like cells and induces in vivo antitumor immunity via TLR4

This study examined the ability of lipopolysaccharide (LPS) to affect glioma and glioma stem-like cells (GSCs) in vitro and to induce antitumor immunity in vivo and the role of TLR4 in these processes.

LPS pretreatment promotes the recognition and eradication of tumor GSCs in vivo when the immune function of the tumor-bearing host is intact. In addition, our data indicate a complex relationship between bacterial infection and glioma prognosis.

Using RT-PCR and immunohistochemistry, we examined the expression of TLR4 in 34 glioblastoma clinical samples. Using real time-PCR, western blot and ELISA analyses, the effect of LPS stimulation on the expression of immune related molecules was evaluated in RG2 and U87 GSCs. Control or LPS-pretreated RG2 GSCs were intracranially or subcutaneously implanted into wild-type or nude Fisher 344 rats. Histopathological examinations were used to assess tumor progression and immune infiltration and Kaplan-Meier analyses to compare survival times of the animal models.

TLR4 was highly expressed in glioblastoma clinical samples. In vitro LPS stimulation for 6 h significantly altered expression of immune related molecules in RG2 and U87 GSCs. However, prolonged LPS stimulation diminished this effect. Rats inoculated intracranially with LPS-pretreated RG2 GSCs survived significantly longer than rats inoculated with control RG2 GSCs. In vivo, LPS-pretreated RG2 GSCs expressed higher levels of MHC molecules, CXCL10 and TNF-α and recruited more CD8+ lymphocytes. However, intratumoral LPS treatment was not equally beneficial. Furthermore, the in vitro and in vivo effects of LPS stimulation appeared to be largely TLR4-dependent.