Biomarkers for immunotherapy for treatment of glioblastoma

Abstract

Immunotherapy is a promising new therapeutic field that has demonstrated significant benefits in many solid-tumor malignancies, such as metastatic melanoma and non-small cell lung cancer. However, only a subset of these patients responds to treatment. Glioblastoma (GBM) is the most common malignant primary brain tumor with a poor prognosis of 14.6 months and few treatment advancements over the last 10 years. There are many clinical trials testing immune therapies in GBM, but patient responses in these studies have been highly variable and a definitive benefit has yet to be identified. Biomarkers are used to quantify normal physiology and physiological response to therapies. When extensively characterized and vigorously validated, they have the potential to delineate responders from non-responders for patients treated with immunotherapy in malignancies outside of the central nervous system (CNS) as well as GBM. Due to the challenges of current modalities of radiographic diagnosis and disease monitoring, identification of new predictive and prognostic biomarkers to gauge response to immune therapy for patients with GBM will be critical in the precise treatment of this highly heterogenous disease. This review will explore the current and future strategies for the identification of potential biomarkers in the field of immunotherapy for GBM, as well as highlight major challenges of adapting immune therapy for CNS malignancies.

Preoperative Predictors of Early Mortality Risk in Isocitrate Dehydrogenase-Wild-Type Glioblastoma Patients Treated with Standard Therapy

“…In recent decades, despite continuous improvements in neurosurgery techniques and innovations in new treatment methods, such as immunotherapy and molecular-targeted therapy, the survival time of patients with GBM is still not optimistic. 2,29,30 It is noteworthy that a certain number of GBM patients with good preoperative and postoperative Abbreviations: NLR, the neutrophil-to-lymphocyte ratio; PLR, the platelet-tolymphocyte ratio; LMR, the lymphocyte -to-monocyte ratio; PNI, the prognostic nutrition index; AGR, albumin-to-globulin ratio; RDW, red blood cell distribution width; GLC, glucose; LDH, lactate dehydrogenase; FIB, fibrinogen; DD, D-dimer. health status, who received standard treatment protocols, should have better clinical outcomes, but instead had an endpoint event ie, death within 1 year.…”

“…In recent decades, despite continuous improvements in neurosurgery techniques and innovations in new treatment methods, such as immunotherapy and molecular-targeted therapy, the survival time of patients with GBM is still not optimistic. 2 , 29 , 30 It is noteworthy that a certain number of GBM patients with good preoperative and postoperative health status, who received standard treatment protocols, should have better clinical outcomes, but instead had an endpoint event ie, death within 1 year. Thus, we focused on IDH-wt GBM patients with preoperative and postoperative KPS scores ≥70 (ECOG PS scores ≥ 1) and receiving standard treatment including GTR, followed by concurrent chemoradiotherapy and adjuvant temozolomide.…”

A Hematological-Related Prognostic Scoring System for Patients With Newly Diagnosed Glioblastoma

“…In recent decades, despite continuous improvements in neurosurgery techniques and innovations in new treatment methods, such as immunotherapy and molecular-targeted therapy, the survival time of patients with GBM is still not optimistic (4,29,30). Accumulating studies have demonstrated that peripheral blood test parameters play a remarkable role in the prognosis of various malignant tumors, such as lung cancer, gastric cancer, colorectal cancer, and hepatocellular carcinoma, as well as GBM (12)(13)(14)(15)(31)(32)(33).…”

Immunotherapy of Glioblastoma: Current Strategies and Challenges in Tumor Model Development

“…Vaccination of glioblastoma patients with a peptide mimicking the EGFR variant III (EGFRvIII) in glioblastoma cells, together with standard temozolomide chemotherapy or the anti-angiogenic agent bevacizumab, showed promising anti-glioblastoma effects in clinical trials. As only 25–30% of patients express EGFRvIII, and its expression is heterogeneous in tumors and unstable through the course of the disease, the efficiency of these vaccines is limited [ 72 , 73 ]. Moreover, a randomized, double-blind, and international phase 3 trial, which assessed the efficacy of the vaccine, based on EGFRvIII-specific peptide (CDX-110), with temozolomide did not show a survival benefit for newly diagnosed glioblastoma patients with EGFRvIII mutation [ 74 ].…”