Abstract 4884: Intratumoral high endothelial venules as a surrogate marker for T cell inflamed tumor microenvironment and prognosis in gastric cancer

Abstract

Abstract The absolute number of tumor infiltrating lymphocyte (TIL) have been well-studied for its prognostic impact in various human malignancies and association with therapeutic response to immune checkpoint blockade, but the importance of its distinct histologic pattern is not yet reported in gastric cancer. Also, the prognostic impact of high endothelial venule (HEV), which is a unique vasculature specialized for lymphocyte extravasation from systemic circulation to target tissue, has not gained much attention despite being believed to play a role in T cell infiltration into solid tumors. Here, we comprehensively analyzed the lymphocytic reaction patterns and HEVs using a large cohort of gastric cancer patients, and investigated their relationship with various clinicopathological features and prognosis. This study included 460 patients who underwent surgical resection for gastric cancer. Three representative TIL patterns was scored from 0 to 3. The definitions of the three patterns are: (1) Crohn-like lymphoid reaction (CLR)-nodular lymphoid aggregate with or without germinal center being observed either inside or along the tumor border; (2) Peritumoral lymphoid reaction (PLR)-band-like lymphocytic infiltration along the invasive margin; (3) Intratumoral lymphoid reaction (ILR)-lymphocytic infiltration into the stroma between cancer cells, or lymphocytes coming into direct contact with cancer cells. Immunohistochemistry for MECA-79 was selected as a specific marker of HEV in this study. Prominent CLR (score 2-3) was significantly associated with diffuse type, advanced stage, or more harvested lymph nodes (P < 0.05, all). Prominent PLR was significantly associated with intestinal type or advanced T stage (P < 0.05, all). Prominent ILR was significantly associated intestinal type or upper 1/3 location (P < 0.05, all). High HEV density was observed at significantly higher frequency in female patients and in tumors with diffuse type or early stage (P < 0.05, all). Notably, the number of HEV was associated with all histologic types of TIL patterns, especially with CLR scores (P < 0.001). In terms of disease-free survival (DFS) and overall survival (OS), patients with high score (score 2-3) of either of the three histologic TIL patterns didn’t show significant difference in survival compared with those with low score (score 0-1). However, the patients with high HEV density showed longer DFS and OS compared with those with low HEV density (both P < 0.001), and this result was consistent even when other variables such as age, sex, stage were adjusted (both P < 0.001). In conclusion, although the results of this study suggest that all three histopathological lymphocyte infiltration patterns are not associated with patient survival, it presents the HEV density as a potential immune related prognostic factor in gastric cancer. Citation Format: Hongjae Chon, So Jung Kong, Joo Hoon Kim, Won Suk Lee, Sewha Kim, Chan Kim. Intratumoral high endothelial venules as a surrogate marker for T cell inflamed tumor microenvironment and prognosis in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4884.