Objective: To evaluate the prognostic value of tumor infiltrating lymphocytes (TILs) in nasopharyngeal carcinoma (NPC) patients. Method: Meta-analysis was performed on eligible studies that was identified by systematic searching of Google scholar, MEDLINE, CNKI, Scopus, PubMed, PMC, Embase and Web of Science databases. The study protocol was registered in International Platform of Registered Systematic Review and Meta-Analysis Protocols-INPLASY (registration number: INPLASY202160014). Databases were searched from inception to January 20, 2020 to identify eligible studies. Those studies that evaluated survival in the form of hazard ratio (HR) in TILs of NPC patients was analyzed. All statistical analysis was performed by using STATA version 16.0 software. Result: Fourteen studies with a total of 3025 patients was analyzed. The pooled result showed that high TILs was significantly associated with favorable overall survival (OS) (HR = 0.55; 95%CI = 0.39-0.77; P = 0.001) and disease free survival (DFS) (HR = 0.60; 95%CI = 0.44-0.81; P = 0.04). Interestingly, high intratumoral TILs had relatively better OS (HR = 0.45; 95%CI = 0.35-0.58; P = 0.006) than stromal TILs (HR = 0.59; 95%CI = 0.36-0.97; P = 0.03). Moreover, an increased level of CD4+ cells infiltration was correlated with favorable OS (HR = 0.4; 95%CI = 0.18-0.85; P = 0.01). CD3+, CD8+ and FoxP3+ lymphocyte’s better prognosis was not statistically significant for OS ( P = 0.09; P = 0.07; P = 0.52) and for DFS ( P = 0.13; P = 0.29) respectively. However, subgroup analysis of intratumoral CD3+ (HR = 0.48; 95%CI = 0.33-0.70; P = 0.05) and intratumoral CD8+ (HR = 0.32; 95%CI = 0.16-0.62; P = 0.001) was significantly associated with improved OS, but not significant in stromal CD3+ (HR = 0.66; 95%CI = 0.20-2.20; P = 0.62). Conclusion: TILs were variably correlated with better prognosis depending on their microanatomic location and subset of TILs in NPC patients. CD4+, intratumoral CD3+ and intratumoral CD8+ lymphocytes could predict favorable patient outcome which suggest that their role in mediating antitumor immune response could potentially be exploited in the treatment of NPC patients. Future large study on the prognostic value of microanatomic location of TILs is needed for confirmation.
Several studies have investigated the prognostic significance of programmed cell death ligand 1 (PD-L1)-positive expression in the tumor cells (TC) of patients with lung cancer. However, tumor-infiltrating immune cell (TIIC)-based PD-L1 expression and its prognostic value remain controversial. The present meta-analysis was performed on 11 studies comprising 2,685 patients, which were identified by a systematic search on the PubMed, PMC, Web of Science and Embase databases. The databases were searched for published articles up to October 30, 2020. The studies that evaluated overall survival (OS) or disease-free survival (DFS) expressed as hazard ratios (HRs) in the PD-L1 TIIC of patients with lung cancer were analyzed. All statistical analyses were conducted using Stata software, version 16.0. The results demonstrated that PD-L1 expression in TIICs was not associated with OS [HR=0.98; confidence interval (CI)=0.73-1.33; P=0.53] and DFS (HR=1.05; CI=0.63-1.77; P=0.42) for all the cohort included in the study. However, subgroup analysis revealed that PD-L1 TIICs were associated with improved OS in lung squamous cell carcinoma (HR=0.76; CI=0.58-0.99; P=0.04), while poorer DFS was observed in lung adenocarcinoma (HR=1.30; CI=1.19-1.43; P=0.008) and at the >1% staining cutoff value (HR=1.56; CI=1.12-2.16; P=0.03). However, poor OS (P=0.21) and DFS (P=0.14) were observed in Asian populations, while DFS (P=0.07) for only-membrane staining was not statistically significant. The results of the present study suggested that adding PD-L1 TIICs to the existing diagnostic algorithm may help to guide patient selection for anti-PD-1/PD-L1 therapy. Future large-scale studies are warranted for confirmation of the present findings.
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