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Expression and regulation of CD276/B7-H3 on bladder tumor lines and somatic urothelial cells

Reitnauer, LE;

Bladder carcinoma is one of the most common types of cancer worldwide. Almost all bladder carcinomas are urothelial cell carcinomas. About half of the cases in Germany belong to the prognostically worse group of invasive bladder carcinomas. These tumors potentially require more intensive therapy due to their greater spread. An important component of such a therapy can be an immunotherapy. PD-1 inhibitors in particular are currently available for urothelial cell carcinoma. Like PD-1, CD276 also belongs to the immunomodular B7 family. The aim of this work was to investigate the expression behavior of CD276 and its regulation on urothelial carcinoma cells and on somatic urothelial cell cultures in order to better understand this potentially therapeutically relevant molecule on urothelial cells. Cell culture experiments and immunofluorescence staining of tissue samples were performed to assess CD276 expression both at the cell level and in the overall histological context. The basic expression of CD276 was very heterogeneous in the cells examined. A variable picture was also revealed when comparing the expression at the transcript level, protein level and on the cell surface. Under different trigger factors such as hypoxia, LPS, PMA and ionomycin, FSL-1 and mycoplasma, there was no change in the expression of CD276 on tumor cell lines and somatic urothelial cell cultures. The evaluation of the immunofluorescence was made more difficult by the inconsistent evaluation strategies of studies already published by other working groups. In this work, no connection between the expression of CD276 and the stage of spread of the tumor or its degree of differentiation could be shown. In contrast, a significantly increased expression of CD276 was found in samples from a patient who had received BCG instillation some time previously. Further studies are needed to validate the results and explore the expression of CD276 on urothelial carcinoma cells.