Abstract B191: The impact of postoperative myeloid-derived suppressor cells on prognosis of gastric cancer patients

Abstract

Abstract Background and Aim: Myeloid cells such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and neutrophils have a suppressive role in the antitumor immunity. In gastric cancer (GC) patients, it has been reported that these myeloid cells in peripheral blood or tumor tissue were associated with their prognosis and increased after surgical treatments. Some reported that the tumor progression and frequent recurrence were caused by increased MDSC after surgical stress in a mouse model. However, in human GC patients, it is still unclear whether such an increase of myeloid cells after gastrectomy is related to their poor prognosis. In this study, we investigate the relationship between the increase of myeloid cells after surgery and prognosis in gastric cancer patients. Materials and Methods: For analysis of relationship between increased myeloid cells after surgery and patients’ prognosis, general archival data were obtained from 278 pStgae2-3 GC patients who received curative resection between January 2007 and December 2014. For analysis of relationship between perioperative changes of MDSCs and patients’ clinicopathologic data, peripheral blood was obtained from 75 GC patients who underwent gastrectomy between April 2016 and December 2017, and MDSCs, CD8, CD4 T-cells, and regulatory T-cells (Tregs) were analyzed by flow cytometry. For analysis of the immunosuppressive function, MDSCs were purified by FACS Aria II and the IFNγ secretion assay were performed using activated autologous T-cells as responder cells. Result and Discussion: In the analysis with 278 GC patients, short RFS was significantly correlated with increased number of monocytes after surgery (#monocytes) (P=0.0073), but not increased number of neutrophils (#neutrophils) (P=0.26). A multivariate analysis demonstrated that #monocytes (HR 1.49; 95% CI 1.01-2.21), pT (HR 2.14; 95% CI 1.26-3.83), pN (HR 2.98; 95% CI 1.81-5.18), postoperative complications (HR 1.69; 95% CI 1.03-2.68) were independently associated with RFS. In the analysis with 75 GC patients, preoperative % M-MDSCs (CD11b+ CD33+ HLA-DR- in CD14+ PBMCs) was positively associated with pathologic stages. After gastrectomy, % M-MDSCs dramatically increased in most patients. On the other hand, % Foxp3+ CD25+ in CD4+ increased but not significantly, while % CD4 and %CD8 in CD3+ were stable. By the suppression assay, smaller number of IFNγ-secreting responder cells were observed when they were co-cultured with M-MDSCs than with CD11b+ CD33+HLA-DR+ cells. Because the increase in the number of M-MDSCs (#M-MDSCs) was positively correlated with #monocytes (r2=0.57 P<0.0001), #M-MDSCs after surgery might be related to poor prognosis of GC patients. Conclusion: The larger number of monocytes after gastrectomy was independently associated with poorer prognosis. The immunosuppressive effect of M-MDSCs increased after surgery could be one of the reasons for the early relapse in gastric cancer patients. Citation Format: Shinya Urakawa, Hisashi Wada, Masaki Mori, Yuichiro Doki. The impact of postoperative myeloid-derived suppressor cells on prognosis of gastric cancer patients [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B191.