A subset of bladder patients does not respond to BCG treatment effectively and the underlying reason behind this observation is currently unclear. CD4+T cells are composed of various subsets that each expresses a distinctive set of cytokines and can potently shift the immune response toward various directions. In this study, we examined the CD4+T-cell cytokine response in bladder cancer patients toward BCG stimulation. We found that bladder cancer patients presented a variety of responses toward BCG, with no uniform characteristics. Those patients with high IFN-γ and IL-21 expression in CD4+T cells presented significantly better prognosis than patients with low cytokine secretion in CD4+T cells. Tumor-infiltrating CD4+T cells were significantly less potent in expressing IFN-γ, IL-4, and IL-17, and more potent in expressing IL-10 than circulating CD4+T cells. In addition, we found no difference in CD80, CD86, or MHC II expression by macrophages from patients with different IFN-γ and IL-21 levels. However, the secretion of IL-12, a Th1-skewing cytokine, was released at significantly higher level by macrophages from patients with high IFN-γ or high IL-21 secretion. We also identified that modulating monocytes/macrophages by GM-CSF-mediated polarization resulted in significantly elevated expression of IFN-γ and IL-21 from CD4+T cells. Overall, these results suggested that the specific types of responses mounted by CD4+T cells were critical to the final outcome of bladder cancer patients and can be influenced by monocyte/macrophage polarization.
Cancer immunology, immunotherapy : CII. 2018 Feb 24 [Epub ahead of print]
Guang Shan, Tian Tang, Huijun Qian, Yue Xia
Departments of Urology II, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei, China. ., Departments of Oncology II, Renmin Hospital of Wuhan University, Wuhan, Hubei, China., Departments of Urology II, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei, China.