Tumor-Infiltrating Lymphocytes in Glioblastoma Are Related to Specific Genomic Alterations

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The role of tumor-infiltrating lymphocytes in glioblastoma has not been fully defined. In a study reported in Clinical Cancer Research, Rutledge and colleagues assessed the association between tumor-infiltrating lymphocytes and molecular alterations, histologies, and survival in glioblastoma.

In the study, histopathologic images from 171 glioblastomas from The Cancer Genome Atlas were used to categorize tumor-infiltrating lymphocytes as absent, present, or abundant, and associations were examined between lymphocytes and histologic features, mutations, copy number alterations, CpG island methylator phenotype, transcriptional class, and survival. Histologic findings were validated using CD3G gene expression.

Strong Associations

A positive correlation was found between tumor-infiltrating lymphocytes and glioblastomas with gemistocytes, sarcomatous cells, epithelioid cells, and giant cells. Lymphocytes were enriched in the mesenchymal transcriptional class and strongly associated with mutations in NF1 and RB1, mutations that are frequent in the mesenchymal class and characteristic of gemistocytic, sarcomatous, epithelioid, and giant cell histologies. 

Tumor-infiltrating lymphocytes were rare in glioblastomas with small cells and oligodendroglioma components and were depleted in the classical transcriptional class and in EGFR-amplified and homozygous PTEN-deleted glioblastomas. These alterations are, in turn, characteristic of glioblastomas with small cells and glioblastomas of the classical transcriptional class. No association of tumor-infiltrating lymphocytes with survival was observed.

The investigators concluded, “[Tumor-infiltrating lymphocytes] were enriched in glioblastomas of the mesenchymal class, strongly associated with mutations in NF1 and RB1 and typical of histologies characterized by these mutations. Conversely, [tumor-infiltrating lymphocytes] were depleted in the classical class, EGFR-amplified, and homozygous PTEN-deleted tumors and rare in histologies characterized by these alterations.” ■

Rutledge WC, et al: Clin Cancer Res 19:4951-4960, 2013.




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