Joo Yeon Kim1, Woo Gyeong Kim1, Chae Hwa Kwon2, Do Youn Park3,4. 1. Department of Pathology, Haeundae Paik Hospital, College of Medicine, Inje University, Busan, South Korea. 2. BioMedical Research Institute, Pusan National University Hospital, 179, Gudeok-ro, Seo-gu, Busan, 49241, South Korea. chkwon@pusan.ac.kr. 3. Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, Busan, South Korea. pdy220@pusan.ac.kr. 4. BioMedical Research Institute, Pusan National University Hospital, 179, Gudeok-ro, Seo-gu, Busan, 49241, South Korea. pdy220@pusan.ac.kr.
Abstract
BACKGROUND: Gastric cancers have been recently classified in accordance with their molecular characteristics, thus demonstrating the complex nature of cancers and an association with the immune contexture within the tumor microenvironment. This study aimed to investigate the correlation between the molecular subtype and immune contexture of gastric cancers. METHODS: The immune contexture, including the type, density, and location of tumor-infiltrating lymphocytes (TILs), of gastric cancer patients was examined and immune subtypes were classified based on it. In particular, PD-L1 expression on tumor cells and TILs and Foxp3+ TILs was assessed in accordance with molecular subtypes. RESULTS: High levels of visual TIL estimates and Foxp3+ TILs were markedly associated with increased overall survival (P = 0.001, P < 0.001, separately). Immune subtypes were associated with tumor size, gross type, depth of invasion, lymph node metastatic status, lymphovascular invasion, perineural invasion, and microsatellite instability status. EBV-positive (C1) and MSI (C2) gastric cancers, considered subtypes with better prognosis, were significantly associated with high TIL levels (P < 0.05). In contrast, epithelial-mesenchymal transition (EMT, C3) gastric cancers with poor overall survival displayed low levels of Foxp3+ TILs. Type II tumors (low level of TILs/low PD-L1 expression) displayed a significant correlation with poor overall survival (P = 0.004) and accounted for the highest proportion in the aberrant p53-expressing (C4) gastric cancers. CONCLUSION: The molecular subtype of gastric cancers is correlated with the immune subtype, including immune contexture and PD-L1 expression, within the tumor microenvironment.
BACKGROUND:Gastric cancers have been recently classified in accordance with their molecular characteristics, thus demonstrating the complex nature of cancers and an association with the immune contexture within the tumor microenvironment. This study aimed to investigate the correlation between the molecular subtype and immune contexture of gastric cancers. METHODS: The immune contexture, including the type, density, and location of tumor-infiltrating lymphocytes (TILs), of gastric cancerpatients was examined and immune subtypes were classified based on it. In particular, PD-L1 expression on tumor cells and TILs and Foxp3+ TILs was assessed in accordance with molecular subtypes. RESULTS: High levels of visual TIL estimates and Foxp3+ TILs were markedly associated with increased overall survival (P = 0.001, P < 0.001, separately). Immune subtypes were associated with tumor size, gross type, depth of invasion, lymph node metastatic status, lymphovascular invasion, perineural invasion, and microsatellite instability status. EBV-positive (C1) and MSI (C2) gastric cancers, considered subtypes with better prognosis, were significantly associated with high TIL levels (P < 0.05). In contrast, epithelial-mesenchymal transition (EMT, C3) gastric cancers with poor overall survival displayed low levels of Foxp3+ TILs. Type II tumors (low level of TILs/low PD-L1 expression) displayed a significant correlation with poor overall survival (P = 0.004) and accounted for the highest proportion in the aberrant p53-expressing (C4) gastric cancers. CONCLUSION: The molecular subtype of gastric cancers is correlated with the immune subtype, including immune contexture and PD-L1 expression, within the tumor microenvironment.
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