Research Papers:

Correlation between lower balance of Th2 helper T-cells and expression of PD-L1/PD-1 axis genes enables prognostic prediction in patients with glioblastoma

Yasuo Takashima, Atsushi Kawaguchi, Tomohiko Kanayama, Azusa Hayano and Ryuya Yamanaka _

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Oncotarget. 2018; 9:19065-19078. https://doi.org/10.18632/oncotarget.24897

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Yasuo Takashima1, Atsushi Kawaguchi2, Tomohiko Kanayama1, Azusa Hayano1 and Ryuya Yamanaka1

1Laboratory of Molecular Target Therapy for Cancer, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan

2Center for Comprehensive Community Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan

Correspondence to:

Ryuya Yamanaka, email: [email protected]

Keywords: glioblastoma; prognosis; helper T-cells; PD-L1; PD-1

Received: September 27, 2017     Accepted: March 06, 2018     Published: April 10, 2018


Common cancer treatments include radiation therapy, chemotherapy including molecular targeted drugs and anticancer drugs, and surgical treatment. Recent studies have focused on investigating the mechanisms by which immune cells attack cancer cells and produce immune tolerance-suppressing cytokines, as well as on their potential application in cancer immunotherapy. We conducted expression profiling of CD274 (PD-L1), GATA3, IFNG, IL12R, IL12RB2, IL4, PDCD1 (PD-1), PDCD1LG2 (PD-L2), and TBX21 (T-bet) using data of 158 glioblastoma multiforme (GBM) patients with clinical information available at The Cancer Genome Atlas. Principal component analysis of the expression profiling data was used to derive an equation for evaluating the status of Th1 and Th2 cells. GBM specimens were divided based on the median of the Th scores. The results revealed that Th1HighTh2Low and Th1LowTh2Low statuses indicated better prognosis than Th1HighTh2High, and were evaluated based on the downregulation of PD-L1, PD-L2, and PD-1. Furthermore, Th2Low divided based on the threshold, as well as CD274Low and PDCD1Low, were associated with good prognosis. In the Th2Low subgroup, 14 genes were identified as potential prognostic markers. Of these, SLC11A1Low, TNFRSF1BLow, and LTBRLow also indicated good prognosis. These results suggest that low Th2 balance and low activity of the PD-L1/PD-1 axis predict good prognosis in GBM. The set of genes identified in the present study could reliably predict survival in GBM patients and serve as useful molecular markers. Furthermore, this set of genes could prove to be novel targets for cancer immunotherapy.

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