title: Immune cell infiltrate differences in pilocytic astrocytoma and glioblastoma: evidence of distinct immunological microenvironments that reflect tumor biology.
abstract: OBJECTIVE
  The tumor microenvironment in astrocytomas is composed of a variety of cell types, including infiltrative inflammatory cells that are dynamic in nature, potentially reflecting tumor biology. In this paper the authors demonstrate that characterization of the intratumoral inflammatory infiltrate can distinguish high-grade glioblastoma from low-grade pilocytic astrocytoma.
  
  
  METHODS
  Tumor specimens from ninety-one patients with either glioblastoma or pilocytic astrocytoma were analyzed at the University of California, San Francisco. A systematic neuropathology analysis was performed. All tissue was collected at the time of the initial surgery prior to adjuvant treatment. Immune cell infiltrate not associated with necrosis or hemorrhage was analyzed on serial 4-μm sections. Analysis was performed for 10 consecutive hpfs and in 3 separate regions (total 30 × 0.237 mm(2)). Using immunohistochemistry for markers of infiltrating cytotoxic T cells (CD8), natural killer cells (CD56), and macrophages (CD68), the inflammatory infiltrates in these tumors were graded quantitatively and classified based on microanatomical location (perivascular vs intratumoral). Control markers included CD3, CD20, and human leukocyte antigen.
  
  
  RESULTS
  Glioblastomas exhibited significantly higher perivascular (CD8) T-cell infiltration than pilocytic astrocytomas (62% vs 29%, p = 0.0005). Perivascular (49%) and intratumoral (89%; p = 0.004) CD56-positive cells were more commonly associated with glioblastoma. The CD68-positive cells also were more prevalent in the perivascular and intratumoral space in glioblastoma. In the intratumoral space, all glioblastomas exhibited CD68-positive cells compared with 86% of pilocytic astrocytomas (p = 0.0014). Perivascularly, CD68-positive infiltrate was also more prevalent in glioblastoma when compared with pilocytic astrocytoma (97% vs 86%, respectively; p = 0.0003). The CD3-positive, CD20-positive, and human leukocyte antigen-positive infiltrates did not differ between glioblastoma and pilocytic astrocytoma.
  
  
  CONCLUSIONS
  This analysis suggests a significantly distinct immune profile in the microenvironment of high-grade glioblastoma versus low-grade pilocytic astrocytoma. This difference in tumor microenvironment may reflect an important difference in the tumor biology of glioblastoma.
authors.affiliation: Department of Neurosurgery, University of California, Los Angeles, California, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Yang
authors.forename: Seunggu J
authors.initials: SJ
authors.lastname: Han
authors.forename: Michael E
authors.initials: ME
authors.lastname: Sughrue
authors.forename: Tarik
authors.initials: T
authors.lastname: Tihan
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Parsa
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001254:Astrocytoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019002:CD56 Antigen / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D005260:Female; D005909:Glioblastoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D059016:Tumor Microenvironment / Q000276:immunology*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019002:CD56 Antigen; D016827:CD8 Antigens; C067980:CD68 antigen, human; D000097382:CD68 Molecule