Abstract
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.
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GS, TT, and YX conceived and designed the study. GS, HQ, and YX conducted the experiments. GS, TT, and YX analyzed the data. GS and TT wrote the paper.
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This study was reviewed and approved by the Internal Review Board of the Renmin Hospital of Wuhan University (No. RHWU10536).
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Shan, G., Tang, T., Qian, H. et al. Certain BCG-reactive responses are associated with bladder cancer prognosis. Cancer Immunol Immunother 67, 797–803 (2018). https://doi.org/10.1007/s00262-018-2127-y
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DOI: https://doi.org/10.1007/s00262-018-2127-y