Immune Checkpoints and Innovative Therapies in Glioblastoma

Romani, Massimo; Pistillo, Maria Pia; Carosio, Roberta; Morabito, Anna; Banelli, Barbara

doi:10.3389/fonc.2018.00464

Cited by 75 publications

(59 citation statements)

References 67 publications

(75 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are various factors responsible for treatment resistance in glioblastomas (Table 4) [8][9][10][11][12][13][14][15]. Hypoxia has been correlated with poor prognosis in cervical cancers, head & neck cancers, soft tissue sarcomas, hepatocellular, gastric and invasive breast cancer [16][17][18][19][20][21].…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological Analysis of HIF-1alpha and TERT on Survival Outcome in Glioblastoma Patients: A Prospective, Single Institution Study

Potharaju¹,

Mathavan²,

Balamurugan³

et al. 2019

J. Cancer

View full text Add to dashboard Cite

Glioblastoma multiforme is a highly malignant and aggressive primary brain tumor with a dismal prognosis. We studied the association of immunohistochemical expression of hypoxia inducible factor-1 alpha (HIF-1α), telomerase reverse transcriptase (TERT), isocitrate dehydrogenase 1 (IDH1) and tumor protein p53 with overall survival (OS) in glioblastoma patients uniformly treated by standard of care, with adequate follow-up. In 87 patient samples studied, 59 were male and 28 were female. The median age was 55 years. The median follow-up was 27.7 months and the median overall survival was 14.9 months. Nuclear staining of HIF-1α was expressed in all samples and scored as strong in 42 (48%) and weak in 45 (52%). Multivariable Cox regression revealed strong HIF-1α expression as an independent poor prognostic factor (Hazard Ratio 2.12, 95% CI 1.20 -3.74, P = 0.01). There was a statistically significant difference in OS (9.8 months vs. 16.3 months) between the "HIF-1α -strong and TERT -strong" and the "HIF-1α -weak and TERT -weak" patient subgroups, as evaluated by Kaplan-Meier analysis (P = 0.005). In our study, HIF-1α expression was an independent predictor of OS. The subgroup of patients with strong expression of both HIF-1α and TERT had the poorest prognosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Clinicopathological Analysis of HIF-1alpha and TERT on Survival Outcome in Glioblastoma Patients: A Prospective, Single Institution Study

Potharaju¹,

Mathavan²,

Balamurugan³

et al. 2019

J. Cancer

View full text Add to dashboard Cite

show abstract

“…Immunotherapy has recently gained more and more attention on fighting against tumors and made a great contribution in treating diverse hard-to-treat tumors such as non-small cell lung cancer and melanoma (7,8), which contributed to extending this therapeutic concept to GBM. However, its clinical efficacy in GBM remains to be further elucidated.…”

Section: Introductionmentioning

confidence: 99%

Development of an Immune Infiltration-Related Prognostic Scoring System Based on the Genomic Landscape Analysis of Glioblastoma Multiforme

Tang

2020

Front. Oncol.

View full text Add to dashboard Cite

Introduction: Glioblastoma multiforme (GBM) is the most common deadly brain malignancy and lacks effective therapies. Immunotherapy acts as a promising novel strategy, but not for all GBM patients. Therefore, classifying these patients into different prognostic groups is urgent for better personalized management. Materials and Methods: The Cell type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was used to estimate the fraction of 22 types of immune-infiltrating cells, and least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to construct an immune infiltration-related prognostic scoring system (IIRPSS). Additionally, a quantitative predicting survival nomogram was also established based on the immune risk score (IRS) derived from the IIRPSS. Moreover, we also preliminarily explored the differences in the immune microenvironment between different prognostic groups. Results: There was a total of 310 appropriate GBM samples (239 from TCGA and 71 from CGGA) included in further analyses after CIBERSORT filtering and data processing. The IIRPSS consisting of 17 types of immune cell fractions was constructed in TCGA cohort, the patients were successfully classified into different prognostic groups based on their immune risk score (p = 1e-10). What's more, the prognostic performance of the IIRPSS was validated in CGGA cohort (p = 0.005). The nomogram also showed a superior predicting value. (The predicting AUC for 1-, 2-, and 3-year were 0.754, 0.813, and 0.871, respectively). The immune microenvironment analyses reflected a significant immune response and a higher immune checkpoint expression in high-risk immune group. Conclusion: Our study constructed an IIRPSS, which maybe valuable to help clinicians select candidates most likely to benefit from immunological checkpoint inhibitors (ICIs) and laid the foundation for further improving personalized immunotherapy in patients with GBM.

show abstract

“…A few immune checkpoint inhibitors have been approved by the FDA for their use in several types of cancer. [ 143 ] This is the case of ipilimumab and tremelimumab (CTLA‐4 inhibitors); nivolumab and pembrolizumab (PD‐1 inhibitors); atezolizumab, avelumab; and durvalumab (PD‐L1 inhibitors). [ 144 ] Chimeric antigen receptor T (CAR‐T) cell therapy is an emerging immunotherapeutic strategy in oncology.…”

Section: Clinical Management Of Glioblastoma: New Diagnosis Opportunimentioning

confidence: 99%

Advances in the Knowledge of the Molecular Biology of Glioblastoma and Its Impact in Patient Diagnosis, Stratification, and Treatment

2020

View full text Add to dashboard Cite

Gliomas are the most common primary brain tumors in adults. They arise in the glial tissue and primarily occur in the brain. Low‐grade tumors of World Health Organization (WHO) grade II tend to progress to high‐grade gliomas of WHO grade III and, eventually, glioblastoma of WHO grade IV, which is the most common and deadly glioma, with a median survival of 12–15 months after final diagnosis. Knowledge of the molecular biology and genetics of glioblastoma has increased significantly in the past few years, giving rise to classification methods that can help in management and stratification of glioblastoma patients. However, glioblastoma remains an incurable disease. Glioblastoma cells have acquired genetic and metabolic adaptations in order to sustain tumor growth and progression, including changes in energetic metabolism, invasive capacity, migration, and angiogenesis, that make it very difficult to find suitable therapeutic targets and to develop effective drugs. The current standard of care for glioblastoma patients is surgery followed by radiotherapy plus concomitant and adjuvant chemotherapy with temozolomide. Although progress in glioblastoma therapies in recent years has been more limited than in other tumors, numerous drugs and targets are being proposed and many clinical trials are underway to develop effective subtype‐specific treatments.

show abstract

Immune Checkpoints and Innovative Therapies in Glioblastoma

Cited by 75 publications

References 67 publications

Clinicopathological Analysis of HIF-1alpha and TERT on Survival Outcome in Glioblastoma Patients: A Prospective, Single Institution Study

Clinicopathological Analysis of HIF-1alpha and TERT on Survival Outcome in Glioblastoma Patients: A Prospective, Single Institution Study

Development of an Immune Infiltration-Related Prognostic Scoring System Based on the Genomic Landscape Analysis of Glioblastoma Multiforme

Advances in the Knowledge of the Molecular Biology of Glioblastoma and Its Impact in Patient Diagnosis, Stratification, and Treatment

Contact Info

Product

Resources

About