High endothelial venule is a surrogate biomarker for T-cell inflamed tumor microenvironment and prognosis in gastric cancer

被引：28

作者：

Park, Hyung Soon ^{[1
]}

Kim, Yoo Min ^{[2
]}

Kim, Sewha ^{[3
]}

Lee, Won Suk ^{[4
]}

Kong, So Jung ^{[4
]}

Yang, Hannah ^{[4
]}

Kang, Beodeul ^{[4
]}

Cheon, Jaekyung ^{[4
]}

Shin, Su-Jin ^{[5
]}

Kim, Chan ^{[4
]}

Chon, Hong Jae ^{[4
]}

机构：

[1] Catholic Univ Korea, Coll Med, Dept Internal Med, Div Med Oncol,St Vincents Hosp, Seoul, South Korea

[2] Yonsei Univ, Dept Surg, Coll Med, Seoul, South Korea

[3] CHA Univ, CHA Bundang Med Ctr, Dept Pathol, Sch Med, Seongnam, Gyeonggi Do, South Korea

[4] CHA Univ, Med Oncol, CHA Bundang Med Ctr, Sch Med, Seongnam, Gyeonggi Do, South Korea

[5] Yonsei Univ, Dept Pathol, Gangnam Severance Hosp, Coll Med, Seoul, South Korea

来源：

JOURNAL FOR IMMUNOTHERAPY OF CANCER | 2021年 / 9卷 / 10期

基金：

新加坡国家研究基金会;

关键词：

tumor microenvironment; gastrointestinal neoplasms; lymphocytes; tumor-infiltrating; neovascularization; pathological; INFILTRATING LYMPHOCYTES; CARCINOMA; DENSITY; HEVS;

D O I：

10.1136/jitc-2021-003353

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background High endothelial venule (HEV) is a specialized vasculature for lymphocyte trafficking. While HEVs are frequently observed within gastric cancer (GC), the vascular-immune interaction between HEV and tumor-infiltrating lymphocytes (TILs) has not been well elucidated. In this study, we aimed to unveil the potential value of HEVs as a surrogate marker for T-cell inflamed immune microenvironment in GC using a large number of prospectively collected surgical specimens of GC. Methods We included 460 patients with GC who underwent surgical resection. Nanostring PanCancer immune profiling was performed to evaluate the immunological phenotype of GCs. HEV density and three distinct patterns of TILs (Crohn-like lymphoid reaction, peritumoral lymphoid reaction, and intratumoral lymphoid reaction) were analyzed for their relationship and evaluated as prognostic factors for relapse-free survival (RFS) and overall survival (OS). Results HEV-high GC revealed increased infiltration by immune cell subsets, including dendritic cells, CD8(+) cytotoxic T cells, and CD4(+) helper T cells. In addition, HEV-high GC demonstrated increased immune-modulating chemokines, type I or II interferon pathway, and immune checkpoints, all of which indicate the inflamed tumor microenvironment (TME). All three distinct patterns of TILs were associated with HEV density. In survival analysis, patients with HEV-high GC displayed significantly longer RFS and OS than those with HEV-low GC (p<0.001 for RFS, p<0.001 for OS). Multivariate analysis demonstrated that HEV was the most significant immunological prognostic factor for RFS (patients with high HEV compared with those with low HEV; HR 0.412, 95% CI 0.241 to 0.705, p=0.001) and OS (HR 0.547, 95% CI 0.329 to 0.909, p=0.02) after adjustment for age, stage, and TIL. Conclusion HEV is the most significant immunological prognosticator for RFS and OS in resected GC, indicating inflamed TME.

引用

页数：12