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Expression of PD-1 and CTLA-4 Are Negative Prognostic Markers in Renal Cell Carcinoma

Immuno-oncological therapy with checkpoint inhibition (CI) has become a new standard treatment in metastatic renal cell carcinoma (RCC), but the prognostic value of the expression of CI therapy target molecules is still controversial. 342 unselected consecutive RCC tumor samples were analyzed regard...

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Autores principales: Kahlmeyer, Andreas, Stöhr, Christine G., Hartmann, Arndt, Goebell, Peter J., Wullich, Bernd, Wach, Sven, Taubert, Helge, Erlmeier, Franziska
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572544/
https://www.ncbi.nlm.nih.gov/pubmed/31137694
http://dx.doi.org/10.3390/jcm8050743
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author Kahlmeyer, Andreas
Stöhr, Christine G.
Hartmann, Arndt
Goebell, Peter J.
Wullich, Bernd
Wach, Sven
Taubert, Helge
Erlmeier, Franziska
author_facet Kahlmeyer, Andreas
Stöhr, Christine G.
Hartmann, Arndt
Goebell, Peter J.
Wullich, Bernd
Wach, Sven
Taubert, Helge
Erlmeier, Franziska
author_sort Kahlmeyer, Andreas
collection PubMed
description Immuno-oncological therapy with checkpoint inhibition (CI) has become a new standard treatment in metastatic renal cell carcinoma (RCC), but the prognostic value of the expression of CI therapy target molecules is still controversial. 342 unselected consecutive RCC tumor samples were analyzed regarding their PD-1, PD-L1, and CTLA-4 expression by immunohistochemistry (IHC). The prognostic values for cancer-specific survival (CSS) and overall survival (OS) were analyzed for those not exposed to CI therapy. The expression of PD-1 in tumor-infiltrating mononuclear cells (TIMC) and PD-L1 in tumor cells was detected in 9.4% and 12.3%, respectively (Immune reactive score (IRS) > 0). Furthermore, PD-L1 expression in TIMC (IRS > 0) and CTLA-4 expression in TIMC (>1% positive cells) was detected in 4.8% and 6.3%. PD-1 expression and CTLA-4 expression were significantly associated with a worse OS and CSS in log rank survival analysis and univariate Cox regression analysis. CTLA-4 expression is a prognostic marker that is independently associated with a worse outcome in multivariate Cox regression analysis in the whole cohort (OS: p = 0.013; CSS: p = 0.048) as well as in a non-metastatic subgroup analysis (OS: p = 0.028; CSS: p = 0.022). Patients with combined CTLA-4 expression and PD-1-expression are at highest risk in OS and CSS. In RCC patients, PD-1 expression in TIMC and CTLA-4 expression in TIMC are associated with a worse OS and CSS. The combination of PD-1 expression in TIMC and CTLA-4 expression in TIMC might identify high risk patients. This is, to our knowledge, the first description of CTLA-4 expression to be a prognostic marker in RCC.
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spelling pubmed-65725442019-06-18 Expression of PD-1 and CTLA-4 Are Negative Prognostic Markers in Renal Cell Carcinoma Kahlmeyer, Andreas Stöhr, Christine G. Hartmann, Arndt Goebell, Peter J. Wullich, Bernd Wach, Sven Taubert, Helge Erlmeier, Franziska J Clin Med Article Immuno-oncological therapy with checkpoint inhibition (CI) has become a new standard treatment in metastatic renal cell carcinoma (RCC), but the prognostic value of the expression of CI therapy target molecules is still controversial. 342 unselected consecutive RCC tumor samples were analyzed regarding their PD-1, PD-L1, and CTLA-4 expression by immunohistochemistry (IHC). The prognostic values for cancer-specific survival (CSS) and overall survival (OS) were analyzed for those not exposed to CI therapy. The expression of PD-1 in tumor-infiltrating mononuclear cells (TIMC) and PD-L1 in tumor cells was detected in 9.4% and 12.3%, respectively (Immune reactive score (IRS) > 0). Furthermore, PD-L1 expression in TIMC (IRS > 0) and CTLA-4 expression in TIMC (>1% positive cells) was detected in 4.8% and 6.3%. PD-1 expression and CTLA-4 expression were significantly associated with a worse OS and CSS in log rank survival analysis and univariate Cox regression analysis. CTLA-4 expression is a prognostic marker that is independently associated with a worse outcome in multivariate Cox regression analysis in the whole cohort (OS: p = 0.013; CSS: p = 0.048) as well as in a non-metastatic subgroup analysis (OS: p = 0.028; CSS: p = 0.022). Patients with combined CTLA-4 expression and PD-1-expression are at highest risk in OS and CSS. In RCC patients, PD-1 expression in TIMC and CTLA-4 expression in TIMC are associated with a worse OS and CSS. The combination of PD-1 expression in TIMC and CTLA-4 expression in TIMC might identify high risk patients. This is, to our knowledge, the first description of CTLA-4 expression to be a prognostic marker in RCC. MDPI 2019-05-24 /pmc/articles/PMC6572544/ /pubmed/31137694 http://dx.doi.org/10.3390/jcm8050743 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kahlmeyer, Andreas
Stöhr, Christine G.
Hartmann, Arndt
Goebell, Peter J.
Wullich, Bernd
Wach, Sven
Taubert, Helge
Erlmeier, Franziska
Expression of PD-1 and CTLA-4 Are Negative Prognostic Markers in Renal Cell Carcinoma
title Expression of PD-1 and CTLA-4 Are Negative Prognostic Markers in Renal Cell Carcinoma
title_full Expression of PD-1 and CTLA-4 Are Negative Prognostic Markers in Renal Cell Carcinoma
title_fullStr Expression of PD-1 and CTLA-4 Are Negative Prognostic Markers in Renal Cell Carcinoma
title_full_unstemmed Expression of PD-1 and CTLA-4 Are Negative Prognostic Markers in Renal Cell Carcinoma
title_short Expression of PD-1 and CTLA-4 Are Negative Prognostic Markers in Renal Cell Carcinoma
title_sort expression of pd-1 and ctla-4 are negative prognostic markers in renal cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572544/
https://www.ncbi.nlm.nih.gov/pubmed/31137694
http://dx.doi.org/10.3390/jcm8050743
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