Immune cell infiltrate differences in pilocytic astrocytoma and glioblastoma: evidence of distinct immunological microenvironments that reflect tumor biology

Laboratory investigation

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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 × 0.237 mm2). 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.

Abbreviation used in this paper: HLA = human leukocyte antigen.

Article Information

Address correspondence to: Andrew T. Parsa, M.D., Ph.D., Department of Neurological Surgery, University of California, San Francisco, 400 Parnassus Avenue, A808, San Francisco, California 94143-0350. email: parsaa@neurosurg.ucsf.edu.

Please include this information when citing this paper: published online June 10, 2011; DOI: 10.3171/2011.4.JNS101172.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Summary data of semiquantitative analysis of immunohistochemistry for inflammatory markers in high-grade glioblastoma.

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    Summary data of semiquantitative analysis of immunohistochemistry for inflammatory markers in low-grade pilocytic astrocytoma.

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    Photomicrographs demonstrating the scoring classification for rare (A), intermediate (B), and extensive (C) inflammatory infiltrates for intratumoral CD68 in glioblastoma. Original magnification × 20.

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    Representative photomicrographs for various inflammatory cell markers as indicated in pilocytic astrocytoma. This is a representative staining of different antigens for the pilocytic astrocytoma group demonstrating the different markers of immune cell infiltrate that were analyzed in the low-grade pilocytic astrocytomas. Original magnification × 20.

  • View in gallery

    Bar graph of CD8 and CD68 immunohistochemistry demonstrating the inflammatory infiltrate differences in intratumoral and perivascular immune cell infiltrate in glioblastoma.

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