Abstract
The tumor microenvironment (TME) is the internal environment of malignant tumor progression, and the host antitumor immune response and normal tissue destruction occur in the TME. Tumor-infiltrating lymphocytes (TIL) is a crucial component of the TME and reflect the host antitumor immune response. The purpose of this study was to discuss the methodology for TIL evaluation and assess the prognostic value of TIL in gastric cancer. In total, we reviewed 1,033 gastrectomy cases between 2002 and 2008 at the Third Affiliated Hospital of Soochow University. To understand the prognostic value of TIL in gastric cancer (GC), TIL were assessed by optical microscopy, and verified by immunohistochemistry. There is no current consensus on TIL scoring in GC. In this study, we discussed a TIL evaluation system that includes an analysis of the amount and percentage of TIL in a tumor. Ultimately, 439 (52.7%) cases showed high levels of TIL and 394 (47.3%) cases had low levels. There was a statistically significant relationship among TIL, tumor size, histological grade, LN metastasis, nerve invasion, tumor thrombus, pTN stage, and WHO subtypes (p < 0.001, respectively). TILhi was a positive significant predictor of overall survival (OS) in Kaplan–Meier survival analysis (P < 0.001) and multivariate Cox regression analysis (HR = 0.431, 95% CI: 0.347–0.534, P < 0.001). After surgery, patients with malignant tumors underwent chemoradiotherapy according to standard therapeutic guidelines based on TNM stage. The TNM scoring system cannot reflect the full information of TME; therefore, TIL can be used as a diagnostic supplement. We constructed a nomogram model that showed more predictive accuracy for OS than pTN stage. In summary, this study proves that high levels of TIL are associated with a positive prognosis and that TIL reflect the protective host antitumor immune response.
Highlights
The tumor microenvironment (TME) is the internal environment of malignant tumor progression, and the host antitumor immune response and normal tissue destruction occur in the TME [1]
There is an international standard of Tumor-infiltrating lymphocyte (TIL) scoring, which was stipulated by the 2014 International TILs Working Group on Breast Cancer [16]
There is no current consensus on TIL evaluation in gastric cancer (GC)
Summary
The tumor microenvironment (TME) is the internal environment of malignant tumor progression, and the host antitumor immune response and normal tissue destruction occur in the TME [1]. Tumor-Infiltrating Lymphocytes in Gastric Cancer component of the TME and reflects the host antitumor immune response [4,5,6]. In some solid tumors, such as ovarian cancer, breast cancer, and colorectal cancer, TIL are crucial for inhibiting cancer progression and have implications for the success of active cancer immunotherapy [7,8,9]. Several studies in gastric cancer suggested that TIL and its components may direct patient selection for immunotherapy and checkpoint blockade therapy [12, 13]. This recommends that the TIL evaluation in daily pathological diagnosis has become more important. The objective of this study aimed to discuss the methodology for the morphologic TIL evaluation and assess TIL scoring in a cohort of 1,033 cases by OS and provide basic data for international TIL scoring of GC
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