Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
Hiroaki Tanaka , Takuya Mori , Kenjiro Kimura , Kazuya Muguruma , Kosei Hirakawa , Masaichi Ohira
Background: Conversion surgery for unresectable advanced gastric cancer has been increasing with the development of chemotherapy. Adjuvant chemotherapy regimens after conversion surgery have not been standardized. The main mechanism of nivolumab is augmentation of antitumor immune response of tumor infiltrating cytotoxic T cells (CTL) to cancer cells, and it has recently been reported that nivolumab therapy before and after chemotherapy is effective in other carcinomas. We previously reported that tertiary lymphoid architecture (TLS) correlates with tumor-infiltrating T cells and is associated with a better prognosis in untreated patients. The purpose of this study was to investigate the relationship between the presence of TLS in the primary tumor and prognosis in patients with gastric cancer who underwent conversion therapy. Methods: We evaluated 52 patients with advanced gastric cancer including 17 patients underwent conversion surgery and 35 patients underwent palliative surgery without prior chemotherapy in our department from 2009 to 2017. The local immune environment and presence of TLS was evaluated by immunohistochemical staining. Results: Intratumoral TLS occurred in 20% of patients with advanced cancer who did not receive chemotherapy before surgery and in 52% of patients who received conversion surgery. And the prognosis of patients with the presence of TLS was better than no TLS. Intratumoral CD8 T-cell infiltration was slightly associated presence of TLS. We had a case in which nivolumab was highly effective and converted to conversion surgery, and a case in which nivolumab was highly effective in patients with recurrence after conversion surgery. TLS was observed in the vicinity of the tumor in these patients. Conclusions: The prognosis was good in the case in which intratumoral TLS was present after conversion surgery. These results suggest that the adjuvant nivolumab therapy may improve the outcome of patients underwent conversion surgery for advanced gastric cancer. These results suggest that peri-tumor TLS is a predictor of nivolumab efficacy in adjuvant therapy after conversion surgery.
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