Scoring System for Tumor-Infiltrating Lymphocytes and Its Prognostic Value for Gastric Cancer

Front Immunol. 2019 Jan 29:10:71. doi: 10.3389/fimmu.2019.00071. eCollection 2019.

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.

Keywords: CD3; gastric cancer; prognosis; tumor microenvironment; tumor-infiltrating lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD3 Complex / immunology
  • Chemoradiotherapy
  • Data Accuracy
  • Female
  • Gastrectomy
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Microscopy
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • Retrospective Studies
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / mortality*
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / surgery
  • Tumor Burden
  • Tumor Microenvironment / immunology

Substances

  • CD3 Complex