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. 2017 Mar 31;6(5):e1310358.
doi: 10.1080/2162402X.2017.1310358. eCollection 2017.

Serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in advanced pancreatic cancer

Stephan Kruger  1 , Marie-Louise Legenstein  1 , Verena Rösgen  1 , Michael Haas  1 , Dominik Paul Modest  1   2 , Christoph Benedikt Westphalen  1 , Steffen Ormanns  3 , Thomas Kirchner  2   3 , Volker Heinemann  1   2 , Stefan Holdenrieder  4   5 , Stefan Boeck  1   2
Affiliations

Serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death ligand 1 (sPD-L1) in advanced pancreatic cancer

Stephan Kruger et al. Oncoimmunology. .

Abstract

Up to now, the efficacy of programmed death protein 1/programmed death ligand 1 (PD-1/PD-L1) blockade in pancreatic cancer (PC) remains uncertain. Serum levels of soluble PD-1 and PD-L1 (sPD-1/sPD-L1) have been reported to be independent prognostic factors in solid tumors susceptible to checkpoint blockade. Provenience, regulation and immunologic function of sPD-1 and sPD-L1 in cancer are poorly understood. To the best of our knowledge, sPD-1 and sPD-L1 have not been measured conjointly in any cancer type yet. In contrast to other tumor entities, sPD-1/sPD-L1 levels did not indicate an adverse outcome in a cohort of 41 patients with advanced PC. We observed a close positive correlation of sPD-L1 levels with sPD-1 in patients with advanced PC, suggesting a common provenience and regulation of sPD-1 and sPD-L1 in cancer patients. Higher sPD-L1 levels were present in patients with elevated C-reactive protein or strong tumoral T cell infiltration, while no correlation of sPD-L1 levels with tumoral PD-L1 expression was found. Our findings indicate that sPD-1 and sPD-L1 are markers of systemic inflammation in (pancreatic) cancer. In a subset of PC patients, elevation in sPD-L1 levels might be caused by an inflammatory tumor type - independent of tumoral PD-L1 expression.

Keywords: Immunotherapy; pancreatic cancer; soluble programmed cell death protein 1; soluble programmed death ligand 1; tumor marker.

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Figures

Figure 1.
Figure 1.
Correlation of sPD-1 and sPD-L1 levels in individual patients with advanced pancreatic cancer (n = 41).
Figure 2.
Figure 2.
Overall survival for patients with high vs. low levels of sPD-1 or sPD-L1 (n = 41).
Figure 3.
Figure 3.
(A) Distribution of sPD-1 (left figure) and sPD-L1 (right figure) in patients with normal vs. elevated CRP. Differences in mean were tested using a Student's t-test, differences in distribution pattern were tested using an F-test. (B) Immunohistochemical staining of PD-L1 in controls (A, B) and exemplary pancreatic cancer tissue (C, D). Magnification = × 200. Scale bars indicate 50 µm. (C) Correlation analysis of sPD-L1 levels with tumoral CD3+ T cell infiltration (left figure) and tumoral PD-L1 expression (right figure) in advanced pancreatic cancer patients; Left figure: Correlation of sPD-L1 with tumoral CD3+ T cell infiltration (tCD3 count), differences between groups were tested using an F-test. Right figure: Correlation of sPD-L1 levels with tumoral PD-L1 expression, Pearson coefficient analysis was used to test for a potential correlation.
See this image and copyright information in PMC

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015; 65:5-29; PMID: 25559415; https://doi.org/10.3322/caac.21254 - DOI - PubMed
    1. Quante AS, Ming C, Rottmann M, Engel J, Boeck S, Heinemann V, Westphalen CB, Strauch K. Projections of cancer incidence and cancer-related deaths in Germany by 2020 and 2030. Cancer Med 2016; 5:2649-56; PMID: 27356493; https://doi.org/10.1002/cam4.767 - DOI - PMC - PubMed
    1. Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, Adenis A, Raoul JL, Gourgou-Bourgade S, de la Fouchardière C et al.. Folfirinox versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364:1817-25; PMID: 21561347; https://doi.org/10.1056/NEJMoa1011923 - DOI - PubMed
    1. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN et al.. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369:1691-703; PMID: 24131140; https://doi.org/10.1056/NEJMoa1304369 - DOI - PMC - PubMed
    1. Feig C, Gopinathan A, Neesse A, Chan DS, Cook N, Tuveson DA. The pancreas cancer microenvironment. Clin Cancer Res 2012; 18:4266-76; PMID: 22896693; https://doi.org/10.1158/1078-0432.CCR-11-3114 - DOI - PMC - PubMed

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