Immune cell infiltrate differences in pilocytic astrocytoma and glioblastoma

Evidence of distinct immunological microenvironments that reflect tumor biology: Laboratory investigation

Isaac Yang, Seunggu (Jude) Han, Michael E. Sughrue, Tarik Tihan, Andrew T. Parsa

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Object. 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 x 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 highgrade glioblastoma versus low-grade pilocytic astrocytoma. This difference in tumor microenvironment may reflect an important difference in the tumor biology of glioblastoma.

Original languageEnglish (US)
Pages (from-to)505-511
Number of pages7
JournalJournal of neurosurgery
Volume115
Issue number3
DOIs
StatePublished - Sep 1 2011
Externally publishedYes

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Tumor Microenvironment
Astrocytoma
Glioblastoma
HLA Antigens
Neoplasms
T-Lymphocytes
San Francisco
Natural Killer Cells
Necrosis
Immunohistochemistry
Macrophages
Hemorrhage

Keywords

  • CD56
  • CD68
  • CD8
  • Glioblastoma
  • Immune cell infiltrate
  • Oncology
  • Pilocytic astrocytoma

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Immune cell infiltrate differences in pilocytic astrocytoma and glioblastoma : Evidence of distinct immunological microenvironments that reflect tumor biology: Laboratory investigation. / Yang, Isaac; Han, Seunggu (Jude); Sughrue, Michael E.; Tihan, Tarik; Parsa, Andrew T.

In: Journal of neurosurgery, Vol. 115, No. 3, 01.09.2011, p. 505-511.

Research output: Contribution to journalArticle

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AU - Tihan, Tarik

AU - Parsa, Andrew T.

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N2 - Object. 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 x 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 highgrade glioblastoma versus low-grade pilocytic astrocytoma. This difference in tumor microenvironment may reflect an important difference in the tumor biology of glioblastoma.

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KW - CD68

KW - CD8

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KW - Immune cell infiltrate

KW - Oncology

KW - Pilocytic astrocytoma

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