BCG downregulates PD1 and PD-L1 expression in bladder cancer cells co-cultivated with peripheral blood mononuclear cells

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Abstract
Purpose: BCG is the standard of care to treat high risk non-muscle invasive bladder cancer (NMIBC), reducing recurrence. PD-L1 is a ligand of the co-inhibitory receptor PD1 that has been shown to be expressed by tumor cells of distinct origin related to unfavorable prognosis. The development of a new class of target drugs that inhibit PD-L1 and PD1 has opened a new perspective for urothelial cancer treatment. Although there are few studies searching for the role of BCG over PD1 and PD-L1, many clinical trials are in course using the immune checkpoint inhibitors together with BCG as a new regime to treat NMIBC. Material and methods: We analyzed the expression of PD1 and PD-L1 using qRT-PCR in RT4 bladder cancer (BCa) epithelial cells co-cultivated with peripheral blood mononuclear cells (PBMC) after treatment with BCG. Results: There was a significantly reduction in PD1 and PD-L1 expression by BCa epithelial cells after BCG treatment. In PBMC PD1 was significantly overexpressed. Conclusion: Our results suggest that one of the mechanisms related to the success of BCG in reducing tumor recurrence in NMIBC may be related to the negative control of PD1 and PD-L1 in tumor cells.

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