Zentralbl Chir 2019; 144(S 01): S88
DOI: 10.1055/s-0039-1694190
Vorträge – DACH-Jahrestagung: nummerisch aufsteigend sortiert
Georg Thieme Verlag KG Stuttgart · New York

The co-expression of CD26 with PD-L1 and the fibrotic tumor stroma renders lung cancer targetable to CD26-inhibition

N Enz
1   Department of Thoracic Surgery, University Hospital Rostock, Rostock, Germany
,
F Janker
2   Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
,
S Andreoli
2   Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
,
C Opelz
2   Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
,
W Weder
2   Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
,
JH Jang
2   Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
,
W Jungraithmayr
1   Department of Thoracic Surgery, University Hospital Rostock, Rostock, Germany
2   Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
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Publikationsverlauf

Publikationsdatum:
04. September 2019 (online)

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    Background:

    CD26/dipeptidyl peptidase 4 (CD26) is a transmembrane multifunctional molecule present on various haematopoetic and somatic cells. It has been shown that CD26 is associated with fibrosis in different diseases. We previously showed that CD26 is highly expressed in human lung adenocarcinoma. Additionally, CD26-inhibition decreased lung cancer growth. We here extended our analysis on the co-expression of CD26 with PD-L1 and the fibrosis driver TGF-β1 in lung tumor microenvironment.

    Materials and Methods:

    Samples from patients with lung malignancies (n = 103) including adenocarcinoma (n = 38), squamous carcinoma (n = 26), lung metastases (n = 14), and others (n = 25) were employed. We correlated expression of CD26 with fibrosis related proteins TGF-β1, TGF-R1, TGF-R2 and immunity related genes PD-L1, PD-1 by RT-qPCR. Expression was confirmed on a protein level for CD26 and TGF-β1 by ELISA and by immunohistochemistry (IHC) for CD26 (n = 80). The CD26 expression on tumor cells was graded 0 to 3.

    Results:

    Adenocarcinoma expressed significantly more CD26 than other thoracic malignancies (n = 80, p = 0.0001). While stage IA adenocarcinoma expresses significantly higher amounts of CD26 compared to stage IIIA (p = 0.0019), levels of CD26 raised in stage IIIB and IV, however, without significance. Furthermore, we found a significant correlation between the gene expression of CD26 on adenocarcinoma for TGF-β1 (p < 0.0001), TGF-R1 (p = 0.0004), and TGF-R2 (p < 0.0001). Also, PD-L1 and PD-1 were significantly correlated with CD26 (p = 0.03, p < 0001 respectively). In squamous carcinoma CD26 expression in the microenvironment was significantly correlated with TGF-β1 (p = 0.6), TGF-R1 (p = 0.0015), TGF-R2 (p < 0.0001) and PD-L1 (p < 0.0001), PD-1(p = 0.5). The co-expression of CD26 and TGF-β1 was additionally confirmed on a protein level.

    Conclusion:

    We could confirm that CD26 is highly expressed in lung adenocarcinomas and that CD26 is co-expressed with pro-fibrotic proteins relevant to tumor microenvironment formation. Moreover, the immune checkpoint protein PD-L1 co-expresses with CD26 in lung cancer. This co-expression supports the potential for the treatment of lung cancer with CD26-inhibitors.

    *equal contribution.


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