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Article

B7-H4 Immune Checkpoint Protein Affects Viability and Targeted Therapy of Renal Cancer Cells

1
Biomarkers in Cancer Unit, Biocruces Bizkaia Health Research Institute, Plaza de Cruces 12, 48903 Barakaldo, Spain
2
Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, 0310 Oslo, Norway
*
Author to whom correspondence should be addressed.
Academic Editor: Anna Julie Peired
Cells 2022, 11(9), 1448; https://doi.org/10.3390/cells11091448
Received: 7 March 2022 / Revised: 16 April 2022 / Accepted: 21 April 2022 / Published: 25 April 2022
(This article belongs to the Special Issue New Insights into Kidney Cancer)
Targeted therapy in combination with immune checkpoint inhibitors has been recently implemented in advanced or metastatic renal cancer treatment. However, many treated patients either do not respond or develop resistance to therapy, making alternative immune checkpoint-based immunotherapies of potential clinical benefit for specific groups of patients. In this study, we analyzed the global expression of B7 immune checkpoint family members (PD-L1, PD-L2, B7-H2, B7-H3, B7-H4, B7-H5, B7-H6, and B7-H7) in human renal cancer cells (Caki-1, A-498, and 786-O cell lines) upon treatment with clinically relevant targeted drugs, including tyrosine kinase inhibitors (Axitinib, Cabozantinib, and Lenvatinib) and mTOR inhibitors (Everolimus and Temsirolimus). Gene expression analysis by quantitative PCR revealed differential expression patterns of the B7 family members in renal cancer cell lines upon targeted drug treatments. B7-H4 gene expression was upregulated after treatment with various targeted drugs in Caki-1 and 786-O renal cancer cells. Knocking down the expression of B7-H4 by RNA interference (RNAi) using small interfering RNA (siRNA) decreased renal cancer cell viability and increased drug sensitivity. Our results suggest that B7-H4 expression is induced upon targeted therapy in renal cancer cells and highlight B7-H4 as an actionable immune checkpoint protein in combination with targeted therapy in advanced renal cancer cases resistant to current treatments. View Full-Text
Keywords: B7-H4; immune checkpoint protein; renal cancer cells; targeted therapies; tyrosine kinase inhibitors; mTOR inhibitors B7-H4; immune checkpoint protein; renal cancer cells; targeted therapies; tyrosine kinase inhibitors; mTOR inhibitors
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MDPI and ACS Style

Emaldi, M.; Nunes-Xavier, C.E. B7-H4 Immune Checkpoint Protein Affects Viability and Targeted Therapy of Renal Cancer Cells. Cells 2022, 11, 1448. https://doi.org/10.3390/cells11091448

AMA Style

Emaldi M, Nunes-Xavier CE. B7-H4 Immune Checkpoint Protein Affects Viability and Targeted Therapy of Renal Cancer Cells. Cells. 2022; 11(9):1448. https://doi.org/10.3390/cells11091448

Chicago/Turabian Style

Emaldi, Maite, and Caroline E. Nunes-Xavier. 2022. "B7-H4 Immune Checkpoint Protein Affects Viability and Targeted Therapy of Renal Cancer Cells" Cells 11, no. 9: 1448. https://doi.org/10.3390/cells11091448

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