Universität zu Köln

Keber, Corinna U., Derigs, Marcus, Schultz, Carolin, Wegner, Moritz ORCID: 0000-0003-0601-9223, Lingelbach, Susanne, Wischmann, Viktoria, Hofmann, Rainer, Denkert, Carsten, Hegele, Axel and Haenze, Joerg (2022). Cellular and soluble immune checkpoint signaling forms PD-L1 and PD-1 in renal tumor tissue and in blood. Cancer Immunol. Immunother., 71 (10). S. 2381 - 2390. NEW YORK: SPRINGER. ISSN 1432-0851

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Abstract

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 gamma (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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Keber, Corinna U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Derigs, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Schultz, Carolin UNSPECIFIED UNSPECIFIED UNSPECIFIED Wegner, Moritz UNSPECIFIED orcid.org/0000-0003-0601-9223 UNSPECIFIED Lingelbach, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Wischmann, Viktoria UNSPECIFIED UNSPECIFIED UNSPECIFIED Hofmann, Rainer UNSPECIFIED UNSPECIFIED UNSPECIFIED Denkert, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Hegele, Axel UNSPECIFIED UNSPECIFIED UNSPECIFIED Haenze, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-673455
DOI:	10.1007/s00262-022-03166-9
Journal or Publication Title:	Cancer Immunol. Immunother.
Volume:	71
Number:	10
Page Range:	S. 2381 - 2390
Date:	2022
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-0851
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EXPRESSION; CARCINOMA; BLOCKADE; CELLS Multiple languages Oncology; Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67345