Whether PD-L1/PD-1 expression plays a significant role in the prognosis of NPC is still controversial. The present study mainly aimed to investigate the prognostic significance of PD-L1/PD-1 expression in patients with NPC. A systematical research was performed in the PubMed, Web of Science, EMBASE, and the Cochrane Library databases up to January 06, 2019. Eighteen studies met eligible criteria were included in the meta-analysis. Quality assessment of included articles was evaluated by Newcastle–Ottawa quality assessment scale (NOS). Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) were used to elucidated the primary endpoint, overall survival (OS), and the secondary endpoints. Furthermore, the relationship between clinicopathological features of NPC and PD-L1/PD-1 expression was estimated by relative ratios (RRs) and 95% CIs. A total of 1836 patients from 15 included studies concerning PD-L1 and 678 patients from six studies regarding PD-1 were included in the meta-analysis. Pooled results revealed that PD-L1 expression in NPC did not correlate with OS (HR 1.34 95% CI 0.93–1.93, p = 0.11), DFS (HR 1.82, 95% CI 0.86–3.85, p = 0.12), PFS (HR 1.19, 95% CI 0.46–3.08, p = 0.72), and DMFS (HR 2.26, 95% CI 0.60–8.56, p = 0.23). Meanwhile, no statistically significant differences existed between the expression level of PD-1 in tumor infiltrating lymphocytes (TILs) and the OS in NPC, with the pooled HR 1.29 (95% CI 0.68–2.42, p = 0.44). In subgroup analysis, higher expression of PD-L1 in immune cells correlated with better OS in patients with NPC, with a pooled HR 0.68 (95% CI 0.47–0.99, p = 0.04). Among the clinicopathological features included in our study, we found that the positive expression of PD-L1 in NPC associated with the higher expression of PD-1 (RR 1.25, 95% CI 1.02–1.52, p = 0.03). Our meta-analysis indicated that higher/positive expression of PD-L1/PD-1 may not serve as suitable biomarkers for the prognosis of NPC, which was not in consistent with some previous studies about the prognostic value of PD-L1/PD-1 in other types of tumors. Despite the positive results in subgroup analysis and study about clinicopathological features, it may still need corroboration of prospective and large-scale studies.

Glioblastoma multiforme (GBM) is a highly aggressive malignancy and represents the most common brain tumor in adults. To better understand its biology for new and effective therapies, we examined the role of GDP-mannose pyrophosphorylase B (GMPPB), a key unit of the GDP-mannose pyrophosphorylase (GDP-MP) that catalyzes the formation of GDP-mannose. Impaired GMPPB function will reduce the amount of GDP-mannose available for O-mannosylation. Abnormal O-mannosylation of alpha dystroglycan (α-DG) has been reported to be involved in cancer metastasis and arenavirus entry. Here, we found that GMPPB is highly expressed in a panel of GBM cell lines and clinical samples and that expression of GMPPB is positively correlated with the WHO grade of gliomas. Additionally, expression of GMPPB was negatively correlated with the prognosis of GBM patients. We demonstrate that silencing GMPPB inhibits the proliferation, migration, and invasion of GBM cells both in vitro and in vivo and that overexpression of GMPPB exhibits the opposite effects. Consequently, targeting GMPPB in GBM cells results in impaired GBM tumor growth and invasion. Finally, we identify that the Hippo/MMP3 axis is essential for GMPPB-promoted GBM aggressiveness. These findings indicate that GMPPB represents a potential novel target for GBM treatment.

Purpose: Platinum-based chemotherapy plus PD-1 inhibitors (chemoimmunotherapy) was the standard systemic treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). However, biomarkers to predict the survival outcomes remained unsatisfying. This study aimed to establish a simple but easily applicable model to predict the survival outcomes of R/M NPC receiving chemoimmunotherapy.Materials and methods: A total of 319 R/M NPC patients treated by chemoimmunotherapy with or without local therapy at our hospital were randomly divided into training (n=223) and validation (n=96) cohorts at a ratio of 7:3. An easily applicable prognostic risk grouping model was created using common independent predictors of progression-free survival (PFS) and overall survival (OS) in the training set. Model performance was assessed in the validation set.Results: Pretreatment IL-6 and EBV DNA levels were identified as independent prognostic factors (scored on 0-4 points), and used to develop a prognostic risk grouping model with distinct survivals: 0-1 point (low risk), 2-3 points (intermediate risk), and 4 points (high risk). In the training set, the median PFS were not reached (NR), 18.90, and 7.73 months (P<0.001) respectively in the low-, intermediate-, and high-risk groups, while the median OS were NR, NR and 13.6 months (P<0.001). Results were further confirmed in the validation set.Conclusion: This model predicted both PFS and OS in R/M NPC patients undergoing chemoimmunotherapy. This finding may help clinicians with an initial prognostic estimation but warrants further prospective investigation for the value of IL-6 and EBV DNA.

Background/Objectives: The efficacy and time-dependent pattern of consolidation immunotherapy after induction chemoimmunotherapy and radiotherapy remain unclear in unresectable stage III non-small cell lung cancer (NSCLC). This study evaluated the efficacy and temporal pattern of consolidation immunotherapy in this population. Methods: This dual-center retrospective cohort study included patients with unresectable stage III NSCLC who achieved disease control after induction chemoimmunotherapy followed by definitive radiotherapy. To reduce potential immortal time bias, only patients who remained alive and progression-free within 2 months after radiotherapy were included. Patients were grouped according to receipt of consolidation immunotherapy. Survival outcomes were analyzed using stabilized inverse probability of treatment weighting, multivariable Cox regression, sequential landmark Cox analysis, and landmark restricted mean survival time analysis. Results: Among 170 eligible patients, 65 received consolidation immunotherapy and 105 did not. After a median follow-up of 33 months, consolidation immunotherapy was associated with longer PFS (hazard ratio [HR]: 0.52, 95% confidence interval [CI]: 0.35–0.78, p = 0.001) and OS (HR: 0.35, 95% CI: 0.18–0.65, p < 0.001). These benefits remained significant after weighting, and multivariable analysis identified consolidation immunotherapy as an independent predictor of improved PFS. Exploratory sequential landmark Cox and restricted mean survival time analyses suggested that the survival benefit was more evident during the early treatment period, particularly around 8–10 months. Conclusions: Consolidation immunotherapy was associated with improved survival, and its benefit appeared more evident during the early treatment period, particularly around 8–10 months. The optimal treatment duration requires further prospective validation.