Mismatch repair status of gastric cancer and association with local and systemic immune response Hyoung-Il Kim1,2*, Su-Jin Shin3, Haeryoung Kim4, Sang Yong Kim2, Chung-Gyu Park5,6, and Woo Jin Hyung1,7 *Corresponding Author 1Department of Surgery, Yonsei University College of Medicine, Yonsei University health System, Seoul, Korea; 2Open NBI Convergence Technology Research Laboratory, Severance Hospital, Yonsei University Health System, Seoul, Korea; 3Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea; 4Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea; 5Translational Xenotransplantation Research Center, Seoul National University College of Medicine; and 6Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea
Background: MSI-high (MSI-H) colorectal cancer is known to be associated with increased tumor-infiltrating lymphocytes (TILs) and good prognosis. In gastric cancer, however, MSI status has rarely been evaluated in accordance with TILs. The objectives of our study were to clarify the relationships between MSI status and antitumor host immune response and to identify the impact of these factors on the prognosis of gastric cancer. Methods: We evaluated 345 patients with gastric cancer who underwent gastrectomy with MSI typing. The numbers of TILs within tumor stroma was counted after immunohistochemical staining with anti-CD3, CD4, CD8, Foxp3, and granzyme B to quantify the subset of TILs. To evaluate systemic immune response, differential white cell count and prognostic nutritional index (PNI) were obtained. Results: Of the 345 patients, 57 were MSI-H and 288 were non-MSI-H groups. MSI-H tumors carried significantly higher numbers of CD8+ T-cells, Foxp3+ T-cells, GZB+ T cells and higher ratio of Foxp3/CD4 and GZB/CD8. The prognostic effect of TILs was different in MSI-H and non-MSI-H groups. All subsets of TILs were not significant prognostic factor for recurrent-free survival (RFS) and overall survival (OS) in MSI-H group. However, in non-MSI-H group, multivariate analysis showed that stage, PNI and CD4+ T cells was independent prognostic factor for RFS and stage, PNI and ratio of Foxp3/CD4 was independent prognostic factor for OS. Conclusions: The number of subset of TILs and the prognostic influence of systemic and local immune response were different between MSI-H and non-MSI-H tumors. The immunogenicity caused by MSI status and subsequent host immune response probably is related to cancer progression and patient prognosis of gastric cancer.
Funding This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIP) (No.2016R1A2B4014984).