Decreased density of CD3+ tumor‐infiltrating lymphocytes during gastric cancer progression

Abstract

Background and Aim: Tumor cells escape host immunosurveillance and thus produce an advantageous environment for tumor progression. Recent studies have demonstrated that tumor-infiltrating lymphocytes (TILs) play a principal role in the immune response to tumors. However, little is understood about numerical alterations in CD3+ TILs during tumor progression in patients with gastric cancer. The present study examines the density of CD3+ TILs to elucidate their clinical significance in gastric cancer. Methods:The numbers of CD3+ TILs in 120 resected specimens from patients with gastric cancer and 27 endoscopic resected specimens from patients with gastric adenoma were immunohistochemically assessed using a CD3 polyclonal antibody. Results: The mean number of CD3+ TILs (± SD) in the patients with gastric cancer and adenoma was 87.5 ± 59.8 and 379.6 ± 128.1, respectively. Significantly more CD3+ TILs were found in specimens from patients with gastric adenoma than with gastric cancer (P < 0.0001). The numbers of CD3+ TILs significantly correlated with depth of tumor invasion, lymph node metastasis, and stage (P = 0.022, P = 0.0004, and P = 0.011, respectively). The 5-year survival rate was significantly poorer for patients with fewer CD3+ TILs (P = 0.004). Multivariate analysis selected the density of CD3+ TILs as an independent prognostic factor (P = 0.034). Conclusions: Our results demonstrated that the density of CD3+ TILs decreases during tumor progression. The density of CD3+ TILs is an immunological predictor of lymph node metastasis and disease outcome in patients with gastric cancer.

Cancer-Associated Fibroblasts Affect Intratumoral CD8+ and FoxP3+ T Cells Via IL6 in the Tumor Microenvironment

“…In contrast, TILs represent the host immune response to tumor proliferation and metastasis (2,28). CD8 þ T cells, which are cytotoxic T lymphocytes (CTLs), demonstrate cytotoxic activity toward tumor cells by triggering apoptosis, and are considered to be the frontline defense against cancer (29)(30)(31)(32). Several recent clinical studies have evaluated the role of TILs as prognostic and predictive factors (11), and have shown that CD8 þ TILs are associated with longer disease-free survival (DFS) and overall survival (OS) in colon and ovarian carcinoma.…”

“…Meanwhile, forkhead box protein 3-positive (FoxP3 þ ) TILs, which are regulatory T cells (Tregs), are thought to suppress mainly antitumor immunity and immunotherapy, as they effectively suppress the proliferation and activation of CTL (30)(31)(32). It is reported that FoxP3 þ TILs are associated with worse prognosis in breast cancer, gastric cancer, and melanoma (29)(30)(31)(32)(33). Furthermore, in esophageal cancer, it has been reported that a stratification based on PD-L1 expression and CD8 þ TIL status is associated with overall survival (34).…”

Association of intra‐tumoral tumour‐infiltrating lymphocytes and neutrophil‐to‐lymphocyte ratio is an independent prognostic factor in non‐small cell lung cancer

“…It is required for T‐cell activation. Although CD3 is an established total T‐cell marker, higher numbers of CD3 + TILs have been associated with a favourable prognosis in patients with several malignancies . Cluster of differentiation 5 (CD5) is constitutively expressed on lymphocyte precursors, on mature T cells and on a subset of mature B cells.…”

Prognostic role of tumor-infiltrating lymphocytes in gastric cancer: a meta-analysis and experimental validation

“…The flow diagram for study selection is shown in Figure 1. Table II summarized the characteristics of all included studies [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. The summarizes should represented by summarized incorporated studies were published from 2003 to 2016 and conducted in China (n = 6), Germany (n = 1), Korea (n = 6), Japan (n = 3), America (n = 1), and Italy (n = 1).…”

“…Eight papers [15,17,20,24,25,27,29,30] investigated the prognostic value of CD3+ TILs in gastric cancer patients. Seven studies [15,20,24,25,27,29,30] researched the connection of CD3+ TILs in the intratumoral site with OS, with a pooled HR of 0.610 for TILs-high cases (95% CI: 0.526-0.708, p < 0.001), without any heterogeneity (Figure 2 B). Only one study [17] reported the CD3+ TILs in tumor stroma (TS) and tumor parenchyma (TP), and the results showed that HRs for DFS were 0.86 (95% CI: 0.33-2.23, p = 0.76) and 0.76 (95% CI: 0.29-1.98, p = 0.58) respectively.…”