Kim EY. J Metab Bariatr Surg. 2022 Dec;11(2):39-48. https://doi.org/10.17476/jmbs.2022.11.2.39

The tumor-associated neutrophils (TANs) value and tumor—stroma ratio (TSR) are promising prognostic parameters in the tumor microenvironment. We aimed to evaluate the prognostic role and relationship of TANs and TSR in gastric cancer. Our study comprised 157 patients who underwent gastrectomy for advanced gastric cancer. TANs were assessed by immunohistochemical staining (CD15 and CD66b) and were analyzed with an image analyzer. TANs have been known to have different functional subpopulations of N1 (anti-tumor) and N2 (pro-tumor). We developed “calculated TANs with pro-tumor function (cN2; CD15 minus CD66b)”. The TSR was evaluated using hematoxylin and eosin staining. High-grade CD15-positive, cN2 in the tumor center, and TSR were significantly related to poor disease-free survival (DFS). TSR and cN2 were independent prognostic factors for DFS (hazard ratio (HR) = 2.614; p = 0.001, HR = 3.976; p = 0.002) and cN2 in the tumor center showed a positive correlation with TSR (R = 0.179, p = 0.025). While CD66b stained both N1 and N2, CD15 detected most of N2. Combining both markers revealed a novel cN2, which was an independent marker of poor prognosis. The transformation from N1 to N2 predominantly occurred in the tumor center, and was associated with TSR.

Kim DJ, et al. J Gastric Cancer. 2024 Dec;25:e8. https://doi.org/10.5230/jgc.2025.25.e8

CD8+ tumor-infiltrating lymphocytes (TILs) play a major role in antitumor immunity. High endothelial venules (HEVs) are related to diverse immune cells in solid tumors. We analyzed CD8+ and Foxp3+ TILs in combination with HEVs to determine their prognostic role in advanced gastric cancer (AGC). We enrolled 157 patients with AGC in this study. The densities of CD8+ TILs and Foxp3+ TILs were calculated using immunohistochemical staining. HEVs were evaluated by MECA-79 expression. HEVs were identified in 60 (38.2%) cases and was significantly associated with an increased number of CD8+ TILs (p = 0.027) but not of Foxp3+ TILs (p = 0.455) and CD20+ TILs (p = 0.163). A high CD8+/HEV+ level was significantly associated with nodal metastasis (p = 0.048). In survival analysis, patients with high CD8+/HEV+ levels demonstrated the longest overall survival (OS) (p = 0.015). Furthermore, a high CD8+/HEV+ level was an independent prognostic factor in AGC (p = 0.011; hazard ratio (HR) = 0.435; 95% confidence interval (CI) = 0.245–0.837). HEVs were found to play an important role in antitumor immunity associated with CD8+ TILs in AGC. This analysis of HEVs and CD8+ TILs helps stratify patients with AGC and sheds light on tumor immunity.

Park KB, et al. J Gastric Cancer. 2019 Apr;19:e34. https://doi.org/10.5230/jgc.2019.19.e34