A Systematic Review of the Tumor-Infiltrating CD8+ T-Cells/PD-L1 Axis in High-Grade Glial Tumors: Toward Personalized Immuno-Oncology

Abstract

Based on preclinical findings, programmed death-ligand 1 (PD-L1) can substantially attenuate CD8⁺ T-cell-mediated anti-tumoral immune responses. However, clinical studies have reported controversial results regarding the significance of the tumor-infiltrating CD8⁺ T-cells/PD-L1 axis on the clinical picture and the response rate of patients with high-grade glial tumors to anti-cancer therapies. Herein, we conducted a systematic review according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statements to clarify the clinical significance of the tumor-infiltrating CD8⁺ T-cells/PD-L1 axis and elucidate the impact of this axis on the response rate of affected patients to anti-cancer therapies. Indeed, a better understanding of the impact of this axis on the response rate of affected patients to anti-cancer therapies can provide valuable insights to address the futile response rate of immune checkpoint inhibitors in patients with high-grade glial tumors. For this purpose, we systematically searched Scopus, Web of Science, Embase, and PubMed to obtain peer-reviewed studies published before 1 January 2021. We have observed that PD-L1 overexpression can be associated with the inferior prognosis of glioblastoma patients who have not been exposed to chemo-radiotherapy. Besides, exposure to anti-cancer therapies, e.g., chemo-radiotherapy, can up-regulate inhibitory immune checkpoint molecules in tumor-infiltrating CD8⁺ T-cells. Therefore, unlike unexposed patients, increased tumor-infiltrating CD8⁺ T-cells in anti-cancer therapy-exposed tumoral tissues can be associated with the inferior prognosis of affected patients. Because various inhibitory immune checkpoints can regulate anti-tumoral immune responses, the single-cell sequencing of the cells residing in the tumor microenvironment can provide valuable insights into the expression patterns of inhibitory immune checkpoints in the tumor micromovement. Thus, administrating immune checkpoint inhibitors based on the data from the single-cell sequencing of these cells can increase patients' response rates, decrease the risk of immune-related adverse events development, prevent immune-resistance development, and reduce the risk of tumor recurrence.

Keywords: PD-L1; glioma; immune checkpoint; personalized medicine; single-cell sequencing; tumor microenvironment; tumor-infiltrating CD8+ T-cells; tumor-infiltrating lymphocytes.