Abstract 796: Impact of histological types on infiltration of regulatory T cells in gastric cancer

Introduction: It is recently known that regulatory T cells (Tregs) are naturally present in the immune system and play important roles of suppression in host's antitumoural immune response. The transcription factor forkhead box P3 (FoxP3) is the most reliable marker for Tregs, and involved in the development and function of Tregs. Previous studies have pointed out that increasing of Tregs were associated with progression of many solid cancers such as breast cancer, melanoma, head and neck cancer, esophageal cancer. However, few reports were found about gastric cancer. Signet ring cell carcinoma with more advanced stage increase the risk of metastasis, like scirrhous carcinoma. It is uuclear whether the number of Tregs is correlated with the progression of signet ring cell carcinoma. The aim of this study is to investigate the population of tumor infiltrating Tregs and the impact of histological types on that in gastric cancer. Materials and methods: A total of 100 patients with gastric cancer who underwent gastrectomy between 2003 and 2008 at our institute were enrolled. FoxP3 expression in primary gastric cancer was analyzed by immunohistochemistry. T cells expressed FoxP3 were defined as Tregs. Results: Our cohort of 100 patitents included almost all histological types of gastric cancer, including tubular adenocarcinoma, poorly differentiated adenocarcinoma, mucinous adenocarcinoma, papillary adenocarcinoma, squamous cell carcinoma, and signet ring cell carcinoma. We detected FoxP3 expression in more than 90% of primary tumors. FoxP3 positive cells infiltrating into tumor were considered as Tregs. The localization of observed infiltrating Tregs expanded to not only tumor but also regional lymph node. The number of Tregs in tumor increased according to the differentiation of the cancer cells. Importantly, we detected significant few tumor infiltrating Tregs in signet ring cell carcinoma compared with the other histological types. On the other hand, signet ring cells themselves expressed FoxP3, indicating that signet ring cells might play a role of suppression of immune response to cancer. Conclusion: We have observed that there were differences between signet ring cell carcinoma and other histological types with regard to the distribution of FoxP3 expression cells. Although the detail clinical investigation is needed, our result suggested that taylor made arrangement associated with histological types should be required for immunotherapy against gastric c