Cancer Management and Research (Jul 2019)
Evaluating the prognostic significance of tumor-infiltrating lymphocytes in solid tumor: practice of a standardized method from the International Immuno-Oncology Biomarkers Working Group
Abstract
Jiu-Yang Liu,1,* Gui-Fang Yang,2,* Fang-Fang Chen,2 Chun-Wei Peng11Department of Gastrointestinal Surgery, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan 430071, People’s Republic of China; 2Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan 430071, People’s Republic of China*These authors contributed equally to this workPurpose: Tumor-infiltrating lymphocytes (TILs) become increasingly relevant to tumor progression. This study aims to evaluate (a) methods of TILs assessment and (b) their prognostic significance in gastric cancer (GC).Methods: The percentage of stromal TILs (psTIL) was reported semi-quantitatively by H&E evaluation. Herein, we screened two independent cohorts of breast cancer (n=240) and GC (n=481) for psTIL characterization. Correlations between psTIL and clinic-pathological features, as well as overall survival (OS) were further explored. Additionally, the prediction role of psTIL in GC was evaluated by receiver operating characteristic curve (ROC) analysis.Results: TILs could be demonstrably distinguished from other stromal areas and surrounding tumor nests according to the assessment method. More importantly, it is reproducible, easily to determine, and quickly performed. In GC, a two-grade scale for psTIL was appropriate to be divided into low and high subgroups by using the median value of 10% as the threshold. High psTIL was correlated with no serosa invasion, earlier TNM stage and better survival state (P<0.05 for all), and identified as a favorable prognostic factor both by univariate (HR: 0.734, P=0.047) and multivariate analyses (HR: 0.722, P=0.030). A beneficial OS of high psTIL was found in a linear manner with increasing TILs infiltrates associated with improved survival by Kaplan–Meier survival curve (P=0.030) and ROC analysis (AUC: 0.432, P=0.012).Conclusion: TILs provide a reproducible method for assessment that can potentially be used to guide management. The parameter psTIL could be served as an independent, favorable prognostic factor of GC.Keywords: tumor-infiltrating lymphocytes, gastric cancer, prognosis, biomarker
