Elevated Proportions of Activated NK Cells at Diagnosis Predict a Favourable Prognosis in Glioblastoma Patients

Despite rapid progress in the treatment of many cancers, glioblastoma remains a devastating disease with dismal prognosis. Recombinant heat shock protein 70 (Hsp70) and IL-2 stimulate the cytolytic activity of NK cells against a large variety of highly aggressive human tumor cells presenting Hsp70 on their cell surface. Therefore, the intra- and extracellular Hsp70 expression was determined in gliomas together with activatory NK cell receptors which are known to interact with membrane-bound Hsp70 (mHsp70). All gliomas are mHsp70-positive and high grade gliomas overexpress Hsp70 in the nucleus and cytosol. Significantly increased extracellular Hsp70 levels are detected predominantly in glioblastomas with large necrotic areas. Overall survival (OS) is improved in patients with low Hsp70 serum levels indicating that high Hsp70 expression levels are associated with unfavorable prognosis. Progression-free survival (PFS) in glioblastoma patients correlates with elevated proportions of activated NK cells (CD56+/CD94+, CD3-/CD69+) at diagnosis. The stimulation of these NK cells in vivo might be related to the presence pro-inflammatory cytokines and the Danger Associated Pattern Molecule (DAMP) Hsp70 in the circulation. Of caution, glucocorticoid therapy reduces the prevalence of activated NK cells. In summary, elevated frequencies of activated NK cells at diagnosis predict a more favorable prognosis in glioblastoma patients.