Abstract
Abstract Background: Given that immune system maintains homeostasis by excluding tumors with mutations, in recent years has been proposed the "cancer-immunoediting" hypothesis, which divides immune responses into three phases, i.e., exclusion, equilibrium, and escape. This equilibrium phase takes likely several decades in human life, during the occurrence of mutations and growth of tumors. Recent studies have emerged that the resident memory T cells (Trm) exclusively survey the transformation of normal tissues in equilibrium phase, though reported were other two memory T subsets in extra-epithelial organs, such as central memory T (Tcm) and effector memory T (Tem) cells. Notably, Trm does not exit into blood circulation, instead exerts powerful ant-tumor functions as tumor infiltrating T cells (TIL), by the expression of unique molecules such as CD69 and CD103; CD69 restricts residence in epithelial tissues, and CD103 bounds to a cognate ligand, epithelial E-cadherin, to stimulate antitumor effect. Purpose: Although previous reports suggested Trm involvement in several tumors, the significance of Trm in predictive patient prognosis of gastrointestinal cancer remains to be investigated fully. Here we study the significance of Trm in colorectal cancer. Materials and Methods: All available patients of hundred-twenty patients with colorectal cancer in Osaka University Hospital were enrolled in this study during 2012 to 2013, under the agreement of written informed consents; the study was performed according to the approval of institutional ethical committee. Immunohistochemistry by staining tissue samples from surgically resected specimens was performed to identify the cellular distribution, number and expression intensity of CD103+/CD69+ in CD8+ lymphocytes, infiltrated in colorectal cancer tissues. Kaplan-Meier analysis and Cox proportional hazards regression models were applied to predict overall and recurrence-free survival in all patients with colorectal cancer examined. Result: The staining of Trm, i.e., intratumor CD103+/CD69+/CD8+ TILs represented a favorable prognostic predictor of overall and recurrence-free survival (p<0.05). Indeed, CD103+ TILs were positively associated with the expression of E-cadherin in intratumor regions of colorectal cancer tissues. Conclusions: The present study suggests that Trm has a significant role in tumor immunity by expressing CD103 in intratumor regions of colorectal cancer tissues, indicating that CD103+ TILs will be useful for the prediction of patient' survival after surgery of colorectal cancer. Citation Format: Masatoshi Kitakaze, Masamitsu Konno, Taroh Satoh, Tsunekazu Mizushima, Yuichiro Doki, Hideshi Ishii. CD103+ tumor infiltrating lymphocytes predict a favorable prognosis in human colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2150.
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