Time-Sequential Change in Immune-Related Gene Expression After Irradiation in Glioblastoma: Next-Generation Sequencing Analysis

Abstract

The time-sequential change in immune-related gene expression of the glioblastoma cell line after irradiation was evaluated to speculate the effect of combined immunotherapy with radiotherapy. The U373 MG glioblastoma cell line was irradiated with 6 Gy single dose. Next-generation sequencing (NGS) transcriptome data was generated before irradiation (control), and at 6, 24, and 48 hours post-irradiation. Immune-related pathways were analyzed at each time period. The same analyses were also performed for A549 lung cancer and U87 MG glioblastoma cell lines. Western blotting confirmed the programmed death-ligand 1 (PD-L1) expression levels over time. In the U373 MG cell line, neutrophil-mediated immunity, type I interferon signaling, antigen cross-presentation to T cell, and interferon-γ signals began to increase significantly at 24 hours and were upregulated until 48 hours after irradiation. The results were similar to those of the A549 and U87 MG cell lines. Without T cell infiltration, PD-L1 did not increase even with upregulated interferon-γ signaling in cancer cells. In conclusions, In the glioblastoma cell line, immune-related signals were significantly upregulated at 24 hours after irradiation. Therefore, the time interval between daily radiotherapy might not be enough to expect full immune responses by combined immune checkpoint inhibitors and newly infiltrating immune cells after irradiation.

Dynamic alterations in PD-1/PD-L1 expression level and immune cell profiles based on radiation response status in mouse tumor model

“…Interestingly, in the early phase, immediately after the initiation of RT, no significant effect was observed. Accordingly, the time interval of 1-2 days was insufficient for RT-induced alterations in the immunologic tumor microenvironment, which is consistent with the results of Kim et al (14). For RT-induced immunogenic cell death, direct tumor cell-killing induces a surge in tumor antigen loading, and related cascade reactions consequently upregulate the expression levels of effector T cells and proinflammatory cytokines (15, 16).…”

Transcriptome alterations in spermatogonial stem cells exposed to bisphenol A

“…The ES is the maximum deviation from zero encountered in the random walk and use corresponding to a weighted Kolmogorov–Smirnov-like statistic. Then, the GSEA results were visualized via the bubble plot using R. The significant gene set is shown through an enrichment plot and heatmap of each gene (Kim et al 2021 ).…”

Human Endogenous Retroviruses: Friends and Foes in Urology Clinics

“…The transcript level peaks at 24 hours after a single dose of gamma-irradiation, ranged from 2.5 to 20 Gy, and returns to baselines within 72 hours. Irradiation triggers expressions of immunity-mediated genes, to which HERV expression may contribute [35]. CAsE-PE cells are an arsenic-transformed human prostate epithelial cell line containing oncogenic mutations in KRAS [36].…”

“…• HERV1: Homologous recombination • Disrupting EYA1 gene in rats [55] • HERV signatures associated with ccRCC prognosis [52] Uterus (female) • SYN-1, SYN-2, SUPYN in placenta [2,3,11,132,133] • HERVs in endometria and pregnancy [135][136][137][138][139][140][141] Prostate (male) • HERV-K (HML-2) [33] • HERV transcription profiles [38][39][40][41] • Irradiation [35] and Arsenic [36] • RT inhibitors [37] • RNase L and OAS [13] Fig. 1.…”