Association of the immune checkpoint molecule expression with neutrophil-lymphocyte ratio in patients with gastric cancer: A retrospective study.

Abstract

48 Background: Programmed cell death (PD) -1, one of immune checkpoint molecules, expresses on T cells and induces immune tolerances in tumor microenvironment by binding to the ligand PDL-1 on the cancer cells. The clinical effect of immune checkpoint inhibitors such as anti-PD-1/PDL-1 antibody was demonstrated in various cancer including malignant melanoma, lung cancer and gastric cancer. The development of biomarkers for case selection that these inhibitors are effective will be in urgent need. We previously showed that neutrophil-lymphocyte ratio (NLR), a marker for general immune response, was related with postoperative recurrence and advanced stage of gastric cancer. In this study, we report the association of pretreatment NLR with PD-1/PDL-1 expression in the primary tumor of gastric cancer. Methods: Using immunohistochemistry, we retrospectively examined the expression of PDL-1 and infiltration of PD-1+ cells in primary tumor from 180 patients who had undergone surgery for gastric cancer between 2007 and 2010 at the Department of Surgical Oncology of Osaka City University. Results: Positive expression of PDL-1 was observed in 78 (43%) patients. PDL-1 expression was correlated with tumor infiltrated PD-1+ cells and related poor prognosis of the patients with Stage II/III. NLR was correlated with pathological stage and lymph node metastasis. In the positive PDL-1 group, NLR was significantly increased compared with negative group. However, the number of infiltrated PD-1+ cells was not correlated with NLR. Conclusions: PDL-1 expression in gastric cancer tissues was associated with pretreatment NLR, indicating that local immune suppression could be reflected in the systemic immune responses. Our data also suggested that NLR might be one of surrogate marker for PD-1/PDL-1 blockade therapy for gastric cancer.