Translational research : the journal of laboratory and clinical medicine
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Prostate cancer growth is controlled by androgen receptor signaling via both androgen-dependent and androgen-independent pathways. Furthermore, the prostate is an immune competent organ with inflammatory changes both within the systemic and local environment contributing to the reprogramming of the prostatic epithelium with consistently elevated lymphocyte infiltration and proinflammatory cytokines being found in prostate cancer. ⋯ However, despite an increase in immune checkpoint inhibitors and inflammatory signaling blockades available for a range of cancer types, we are yet to see substantial progress in the treatment of prostate cancer. Therefore, this review aims to summarize the tumor microenvironment and its impact on androgen receptor signaling in prostate cancer.
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T cells infiltrating lymphedematous tissues have a mixed T helper 1 (Th1) and Th2 differentiation profile. Treatment with neutralizing antibodies targeting cytokines that promote Th2 differentiation (interleukin 4 [IL-4] and IL-13) decreases the severity of lymphedema in preclinical models, suggesting that Th2 cells play a key role in the pathology of this disease. However, these previous studies do not address the contribution of Th1 cells and it remains unknown if IL-4 and IL-3 blockade acts primarily on T cells or decreases the pathological changes of lymphedema by other mechanisms. ⋯ In contrast, mice with defective Th1 cell generation (T-betKO) develop disease with the same severity as wild-type controls. Taken together, our results suggest that Th2 differentiation is necessary for development of lymphedema following lymphatic injury and that Th1 differentiation does not significantly contribute to the pathology of the disease. Such findings are important as immunotherapy directed at Th2 cells has been found to be effective in well-studied Th2-mediated diseases such as asthma and atopic dermatitis and may therefore be similarly useful for lymphedema management.