Prognostic Value of Tumor Infiltrating Lymphocytes in Nasopharyngeal Carcinoma Patients: Meta-Analysis

Abstract

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.

Combining the guidelines and multiphoton imaging methods to improve the prognostic value of tumor‐infiltrating lymphocytes in breast cancer

“…The same to anorectal malignant melanoma, high levels of TILs had significantly better outcomes compared with low levels, and bTILs had a significantly better OS than aTILs and nbTILs [26]. In nasopharyngeal carcinoma, high levels of TILs were significantly associated with favorable OS and DFS, and high levels of TILs in the intratumor have relatively better OS than that in the stroma [27]. Likewise, high levels of TILs were also found to be associated with a positive prognosis in cholangiocarcinoma [28], and endometrial cancer [29].…”

Prognostic role of different PD-L1 expression patterns and tumor-infiltrating lymphocytes in high-grade serous ovarian cancer: a systematic review and meta-analysis

“…Several studies demonstrated that there was no significant correlation between CD4 + TILs and prognosis in patients with hepatocellular carcinoma, esophagus cancer, and colorectal cancer ( 52 – 54 ). Conversely, in pancreatic, nasopharyngeal, lung, and bile duct cancers, elevated levels of CD4 + TILs have been shown to improve patient survival ( 50 , 55 – 57 ). Our findings support the hypothesis that the presence of CD4 + TILs in patients with HGSOC can serve as a predictor for an improved survival.…”

Platelet to Lymphocytes Ratio to Predict Nasopharyngeal Carcinoma Progressivity

“…Barely et al study found that TIL was associated with an increase in overall survival (OS) in NPC patients. PLR does not describe the activity of suppressing the progression of the primary tumor because the PLR value is derived from the bloodstream, whereas the body's immune response to the tumor occurs in the tumor due to the infiltration of immune cells such as neutrophils, eosinophils, basophils, monocytes/macrophages, dendritic cells, NKC, and lymphocytes [22], [23].…”