Regulatory T cells and M2 macrophages present diverse prognostic value in gastric cancer patients with different clinicopathologic characteristics and chemotherapy strategies

J Transl Med. 2019 Jun 7;17(1):192. doi: 10.1186/s12967-019-1929-9.

Abstract

Background: Gastric cancer (GC) remains a refractory cancer worldwide. Currently, exploring the differences of the immune status in GC patients with different subgroups might provide promising immunotherapeutic approaches for the treatment of GC.

Methods: In this study, a total of 598 surgically resected FFPE primary gastric cancer samples were assessed for FOXP3, CD163, CD3, CD8, and PD-L1 markers. The correlations between the immune markers expression and clinicopathological features and prognosis were investigated retrospectively.

Results: In general, PD-L1, CD3, and CD8 could be regarded as favorable prognostic factors. Our data demonstrated that high infiltration of FOXP3+ Treg indicates better prognosis in stage I-II patients, while the converse outcome was noted in stage III-IV patients. Our data also confirmed different prognostic value in different pathological classifications, chemotherapy strategies, and locations, with or without lymph node metastasis. Also, M2 macrophages indicated poor prognosis in general. However, high M2 macrophage infiltration suggests a favorable prognosis in signet ring cell carcinoma and mucinous adenocarcinoma. Moreover, the prognostic value of the two indices when they are combined is reported.

Conclusions: These results suggested that different immune statuses are exhibited in different subgroups of GC, which may direct further understanding of the immune status of GC as well as provide a further theoretical basis and potential targets for GC immunotherapy.

Keywords: FOXP3+ regulatory T cell; Gastric carcinoma; M2 macrophage; Prognosis; Subgroups.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / immunology
  • Adenocarcinoma / mortality
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / physiology*
  • Female
  • Humans
  • Lymphatic Metastasis
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Macrophages / pathology
  • Macrophages / physiology*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Retrospective Studies
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / surgery
  • Survival Analysis
  • T-Lymphocytes, Regulatory / pathology
  • T-Lymphocytes, Regulatory / physiology*
  • Tumor Microenvironment / immunology

Substances

  • Biomarkers, Tumor