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 1 , Atsushi Kawaguchi 2 , Tomohiko Kanayama 1 , Azusa Hayano 1 and Ryuya Yamanaka 1 1 Laboratory of Molecular Target Therapy for Cancer, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan 2 Center for Comprehensive Community Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan Correspondence to: Ryuya Yamanaka, email: ryaman@koto.kpu-m.ac.jp Keywords: glioblastoma; prognosis; helper T-cells; PD-L1; PD-1 Received: September 27, 2017      Accepted: March 06, 2018      Published: April 10, 2018 ABSTRACT 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 Th1 High Th2 Low and Th1 Low Th2 Low statuses indicated better prognosis than Th1 High Th2 High , and were evaluated based on the downregulation of PD-L1, PD-L2, and PD-1. Furthermore, Th2 Low divided based on the threshold, as well as CD274 Low and PDCD1 Low , were associated with good prognosis. In the Th2 Low subgroup, 14 genes were identified as potential prognostic markers. Of these, SLC11A1 Low , TNFRSF1B Low , and LTBR Low 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.