Abstract 1468: Intratumoral tertiary lymphoid structures are associated with favorable prognosis of patients with gastric cancer
Authors: Sakimura Chie , Tanaka Hiroaki , Tamura Tatsuro , Ohira Go , Shibutani Masatsune , Yamazoe Sadaaki , Sakurai Katsunobu , Nagahara Hisashi , Kimura Kenjiro , Toyokawa Takahiro , Amano Ryosuke , Kubo Naoshi , Muguruma Kazuya , Maeda Kiyoshi , Ohira Masaichi , Hirakawa Kosei 
Published: July 2016

Abstract
Background: The host immune system is one of the key players of anti-tumor functions. High numbers of tumor infiltrating lymphocytes has been showed to be a predictor of favorable clinical outcome in several solid cancers. The role of B cells in tumor microenvironment is still unclear. Recent studies have reported a correlation between the densities of B cells and the favorable clinical outcome of cancer patients. Moreover, some studies considered the organization of tumor infiltrating B cells as criteria in addition to the cell density. Tertiary lymphoid structures (TLSs) are defined as transient ectopic lymphoid organizations that can develop in non-lymphoid tissues at the site of chronic inflammation, and are anatomically and functionally similar to secondary lymphoid organs. In the present study, we investigated the association between tumor infiltrating B cells and clinicopathological features in gastric cancer.
Materials and Methods: Tumor blocks were obtained from 226 patients with stage Ib to stage IV gastric cancer who had undergone initial surgical resection. The density of CD20+ B cells within the tumor and invasive margin area was assessed by immunohistochemistry. We also evaluated CD3+ T cells, CD21+ follicular dendritic cells (FDCs), Bcl6 germinal center B cells, and PNAd+ high endothelial venules (HEVs) to show the presence of TLSs in gastric cancer.
Results: Tumor infiltrating B cells mostly organized clusters surrounded by CD3+ T cells. B cell area contained FDCs and some clusters had Bcl6+ B cells. There were HEVs around follicles. We observed most of TLSs at the tumor invasive margin. Kaplan-Meier survival analysis showed that high number of CD20+ B cells was associated with significantly better survival (P&lt;0.0001). Univariate analysis demonstrated a correlation between CD20 high and longer OS, and multivariate analysis also showed that CD20 high was one of the independent predictors of OS.
Conclusion: We demonstrated that B cells mostly infiltrated as TLSs and were associated with better prognosis in patients with gastric cancer. Our results suggested that B cells, perhaps as the structure of TLSs, might play an important role for immune response against gastric cancer.
Citation Format: Chie Sakimura, Hiroaki Tanaka, Tatsuro Tamura, Go Ohira, Masatsune Shibutani, Sadaaki Yamazoe, Katsunobu Sakurai, Hisashi Nagahara, Kenjiro Kimura, Takahiro Toyokawa, Ryosuke Amano, Naoshi Kubo, Kazuya Muguruma, Kiyoshi Maeda, Masaichi Ohira, Kosei Hirakawa. Intratumoral tertiary lymphoid structures are associated with favorable prognosis of patients with gastric cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1468.