The dismal prognoses suffered by malignant primary brain tumor (glioma) patients remain

unchanged over the past two decades despite significant improvements in the treatment of

distinct tumors. Immunotherapy, and vaccine therapy in particular, represents a promising

experimental approach to treat malignant gliomas, but major challenges still remain to

render vaccination clinically effective. These challenges include diminishing the risk of

pathologic autoimmunity, identifying the cellular basis of clinical vaccine benefits, and

increasing the proportion of patients experiencing such benefits. Recent studies in glioma

patients have characterized tumor antigens on human gliomas, identified some of the

immune cells involved in beneficial anti-glioma immunity, and examined how gliomas may

be altered by sub-lethal immune influences, providing a glimpse of the strength to which

immunity influences glioma clinical outcome, and hope that clinically effective vaccines to

treat these tumors are within reach. Insight into the complex dynamics of immune-tumor

interactions promises to extend this reach by delineating mechanisms of immune synergy

with other forms of treatment.