Immune infiltration, glioma stratification, and therapeutic implications

By definition, gliomas are brain tumors emanating from glial precursor cells. Gliomas include glioblastoma (GBM), astrocytoma, oligodendroglioma, and ependymoma. The World Health Organization (WHO) traditionally classifies brain tumors according to their pathological features, with GBM having the highest grade (IV), while lower grades (mostly II, III) are typically assigned to various types of astrocytic, oligodendroglial, and ependymal tumors (1), which collectively are referred to as lower grade gliomas (LGG). In the latest NCI SEER (Surveillance, Epidemiology, and End Results) report and projection, the estimated 2016 incidence and deaths for brain and other CNS tumors is 23,770 and 16,050, respectively (2). According to CBTRUS (Central Brain Tumor Registry of the United States), glioma represents about 27% of all, and 80% of malignant brain and CNS tumors (3). The majority (55.1%) of gliomas are classified as GBMs. For GBMs, the current standard of care consists of surgical resection, radiotherapy with chemotherapy (temozolomide or TMZ). The median survival rate, which ranges from 14.5 to 16.6 months [see (4,5) for review], remains dismally poor despite decades of research and discoveries, leading up to the current era of genomics, targeted therapeutics, and immunotherapeutics. LGGs on the other hand have more favorable clinical outcome, especially cases possessing IDH mutation and co-deletion of 1p and 19q chromosomal arms.