Cellular and soluble immune checkpoint signaling forms PD-L1 and PD-1 in renal tumor tissue and in blood
| العنوان: | Cellular and soluble immune checkpoint signaling forms PD-L1 and PD-1 in renal tumor tissue and in blood |
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| المؤلفون: | Corinna U. Keber, Marcus Derigs, Carolin Schultz, Moritz Wegner, Susanne Lingelbach, Viktoria Wischmann, Rainer Hofmann, Carsten Denkert, Axel Hegele, Jörg Hänze |
| المصدر: | Cancer Immunology, Immunotherapy. 71:2381-2389 |
| بيانات النشر: | Springer Science and Business Media LLC, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, Oncology, Programmed Cell Death 1 Receptor, Immunology, Humans, Immunology and Allergy, RNA, Messenger, Carcinoma, Renal Cell, B7-H1 Antigen, Kidney Neoplasms |
| الوصف: | Immune checkpoint blockade therapy is a treatment option of various metastatic cancer diseases including renal cell carcinoma (RCC). Approved antibody drugs target the co-inhibitory signaling of Programmed Cell Death Ligand-1 (PD-L1) and its receptor Programmed Cell Death-1 (PD-1). The combined evaluation of PD-L1 and PD-1 at the mRNA and protein levels in tumor tissue with differentiation of tumor and immune cells as well as of soluble forms (sPD-L1) and (sPD-1) in blood is of basic interest in assessing biomarker surrogates. Here, we demonstrate that PD-L1 determined as fraction of stained tumor cells (TPS-score) correlates with PD-L1-mRNA in tumor tissue, reflecting the predominant expression of PD-L1 in tumor cells. Conversely, PD-1 in immune cells of tumor tissue (IC-score) correlated with PD-1-mRNA tissue levels reflecting the typical PD-1 expression in immune cells. Of note, sPD-L1 in blood did not correlate with either the TPS-score of PD-L1 or with PD-L1-mRNA in tumor tissue. sPD-L1 released into the supernatant of cultured RCC cells closely followed the cellular PD-L1 expression as tested by interferon γ (IFNG) induction and siRNA knockdown of PD-L1. Further analysis in patients revealed that sPD-L1 significantly increased in blood following renal tumor resection. In addition, sPD-L1 correlated significantly with inflammation marker C-reactive protein (CRP) and with PD-L1 mRNA level in whole blood. These results indicate that the major source of sPD-L1 in blood may be peripheral blood cells and not primarily tumor tissue PD-L1. |
| تدمد: | 1432-0851 0340-7004 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::263af2218487804518b57d8564e5d515 https://doi.org/10.1007/s00262-022-03166-9 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....263af2218487804518b57d8564e5d515 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14320851 03407004 |
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