Investigate the Role of Neutrophil in Different Phenotypes of Upper Tract Urothelial Carcinoma
Cheng-Huang Shen1, Chia-Bin Chang1, Pi-Che Chen1 Chang-Yu, Tsai1, Yang Kai Wu1,ShuFen Wu2
1Department of Urology, Chiayi Christian Hospital,Chiayi, Taiwan; 2National Chung Cheng University, Chiayi, Taiwan;
Upper tract urothelial carcinoma (UTUC) exhibits invasive tumor at diagnosis, and the incidence of UTUC in all urothelial cancers is higher in Taiwan. High ratio of neutrophil-to-lymphocytes is associated with a poor clinical outcome in various cancer including urothelial carcinoma. Tumor associated neutrophils promote tumor progression and also suppress anti-tumor immune responses. In the present study, we would investigate whether neutrophils modulate T cell activation in UTUC.
Materials and Methods:
Peripheral blood of clinical UTUC patients and healthy subjects were collected, and the cell markers were analyzed after specific antibodies conjugated fluorescence dye staining using flow cytometry. Freshly isolated neutrophils co-cultured with CD4+ T cells supplied by healthy donor. In co-culture experiments, additional UTUC tumor tissue culture supernatant was added to mimic the tumor microenvironment.
In peripheral blood, the proportion of neutrophil from UTUC patients was significantly higher than that from healthy subjects. In the co-culture experiment, UTUC neutrophils caused lower CD4+ T cell proliferation, as well as IFN- and IL-2 secretion, compared with healthy neutrophils. Furthermore, healthy neutrophils could reduce the CD4 T proliferation when they pre-treated with UTUC tumor tissue culture supernatant.
These results suggest that neutrophil serve as a mediator for CD4 T inhibition in UTUC.