Caroline E Nunes-Xavier1,2, Wanja Kildal3, Andreas Kleppe3,4, Håvard E Danielsen3,4,5, Håkon Waehre3, Roberto Llarena6, Gunhild M Maelandsmo1, Øystein Fodstad1,7, Rafael Pulido2,8, José I López2,9. 1. Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. 2. Biomarkers in Cancer Unit, Biocruces Bizkaia Health Research Institute, Barakaldo, Spain. 3. Institute for Cancer Genetics and Informatics, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway. 4. Department of Informatics, University of Oslo, Oslo, Norway. 5. Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford, UK. 6. Department of Urology, Cruces University Hospital, Barakaldo, Spain. 7. Faculty of Medicine, Institute for Clinical Medicine, University of Oslo, Oslo, Norway. 8. IKERBASQUE, Basque Foundation for Science, Bilbao, Spain. 9. Department of Pathology, Cruces University Hospital, Barakaldo, Spain.
Abstract
BACKGROUND: Novel immune checkpoint-based immunotherapies may benefit specific groups of prostate cancer patients who are resistant to other treatments. METHODS: We analyzed by immunohistochemistry the expression of B7-H3, PD-L1/B7-H1, and androgen receptor (AR) in tissue samples from 120 prostate adenocarcinoma patients treated with radical prostatectomy in Spain, and from 206 prostate adenocarcinoma patients treated with radical prostatectomy in Norway. RESULTS: B7-H3 expression correlated positively with AR expression and was associated with biochemical recurrence in the Spanish cohort, but PD-L1 expression correlated with neither of them. Findings for B7-H3 were validated in the Norwegian cohort, where B7-H3 expression correlated positively with Gleason grade, surgical margins, seminal vesicle invasion, and CAPRA-S risk group, and was associated with clinical recurrence. High B7-H3 expression in the Norwegian cohort was also consistent with positive AR expression. CONCLUSION: These results suggest distinct clinical relevance of the two immune checkpoint proteins PD-L1 and B7-H3 in prostate cancer. Our findings highlight B7-H3 as an actionable novel immune checkpoint protein in prostate cancer.
BACKGROUND: Novel immune checkpoint-based immunotherapies may benefit specific groups of prostate cancer patients who are resistant to other treatments. METHODS: We analyzed by immunohistochemistry the expression of B7-H3, PD-L1/B7-H1, and androgen receptor (AR) in tissue samples from 120 prostate adenocarcinoma patients treated with radical prostatectomy in Spain, and from 206 prostate adenocarcinoma patients treated with radical prostatectomy in Norway. RESULTS: B7-H3 expression correlated positively with AR expression and was associated with biochemical recurrence in the Spanish cohort, but PD-L1 expression correlated with neither of them. Findings for B7-H3 were validated in the Norwegian cohort, where B7-H3 expression correlated positively with Gleason grade, surgical margins, seminal vesicle invasion, and CAPRA-S risk group, and was associated with clinical recurrence. High B7-H3 expression in the Norwegian cohort was also consistent with positive AR expression. CONCLUSION: These results suggest distinct clinical relevance of the two immune checkpoint proteins PD-L1 and B7-H3 in prostate cancer. Our findings highlight B7-H3 as an actionable novel immune checkpoint protein in prostate cancer.
Authors: Caroline E Nunes-Xavier; Janire Mingo; Maite Emaldi; Karine Flem-Karlsen; Gunhild M Mælandsmo; Øystein Fodstad; Roberto Llarena; José I López; Rafael Pulido Journal: Front Oncol Date: 2022-05-25 Impact factor: 5.738
Authors: Adrianna A Mendes; Jiayun Lu; Harsimar B Kaur; Siqun L Zheng; Jianfeng Xu; Jessica Hicks; Adam B Weiner; Edward M Schaeffer; Ashley E Ross; Steven P Balk; Mary-Ellen Taplin; Nathan A Lack; Emirhan Tekoglu; Janielle P Maynard; Angelo M De Marzo; Emmanuel S Antonarakis; Karen S Sfanos; Corinne E Joshu; Eugene Shenderov; Tamara L Lotan Journal: Cancer Date: 2022-03-25 Impact factor: 6.921