Datta, Rabi R., Schran, Simon ORCID: 0000-0002-1092-9804, Persa, Oana-Diana, Aguilar, Claire, Thelen, Martin ORCID: 0000-0002-2785-9726, Lehmann, Jonas, Garcia-Marquez, Maria A., Wennhold, Kerstin, Preugszat, Ella, Zentis, Peter ORCID: 0000-0002-6999-132X, Von Bergwelt-Baildon, Michael S., Quaas, Alexander, Bruns, Christiane J., Kurschat, Christine, Mauch, Cornelia, Loeser, Heike, Stippel, Dirk L. and Schloesser, Hans A. (2022). Post-transplant Malignancies Show Reduced T-cell Abundance and Tertiary Lymphoid Structures as Correlates of Impaired Cancer Immunosurveillance. Clin. Cancer Res., 28 (8). S. 1712 - 1724. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1557-3265

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Abstract

Purpose: An increased risk to develop cancer is one of the most challenging negative side effects of long-term immunosuppression in organ transplant recipients and impaired cancer immunosur-veillance is assumed as underlying mechanism. This study aims to elucidate transplant-related changes in the tumor immune micro-environment (TME) of cancer. Experimental Design: Data from 123 organ transplant recipients (kidney, heart, lung, and liver) were compared with historic data from non-immunosuppressed patients. Digital image analysis of whole-section slides was used to assess abundance and spatial distribution of T cells and tertiary lymphoid structures (TLS) in the TME of 117 tumor samples. Expression of programmed cell death 1 ligand 1 (PD-L1) and human-leucocyte-antigen class I (HLA-I) was assessed on tissue microarrays. Results: We found a remarkably reduced immune infiltrate in the center tumor (CT) regions as well as the invasive margins (IM) of post-transplant cancers. These differences were more pronounced in the IM than in the CT and larger for CD8 thorn T cells than for CD3 thorn T cells. The Immune-score integrating results from CT and IM was also lower in transplant recipients. Density of TLS was lower in cancer samples of transplant recipients. The fraction of samples with PD-L1 expression was higher in controls whereas decreased expression of HLA-I was more common in transplant recipients. Conclusions: Our study demonstrates the impact of immunosup-pression on the TME and supports impaired cancer immunosurveil-lance as important cause of post-transplant cancer. Modern immu-nosuppressive protocols and cancer therapies should consider the distinct immune microenvironment of post-transplant malignancies.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Datta, Rabi R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schran, SimonUNSPECIFIEDorcid.org/0000-0002-1092-9804UNSPECIFIED
Persa, Oana-DianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aguilar, ClaireUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thelen, MartinUNSPECIFIEDorcid.org/0000-0002-2785-9726UNSPECIFIED
Lehmann, JonasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Marquez, Maria A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wennhold, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Preugszat, EllaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zentis, PeterUNSPECIFIEDorcid.org/0000-0002-6999-132XUNSPECIFIED
Von Bergwelt-Baildon, Michael S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Quaas, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruns, Christiane J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kurschat, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mauch, CorneliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loeser, HeikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stippel, Dirk L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schloesser, Hans A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-673031
DOI: 10.1158/1078-0432.CCR-21-3746
Journal or Publication Title: Clin. Cancer Res.
Volume: 28
Number: 8
Page Range: S. 1712 - 1724
Date: 2022
Publisher: AMER ASSOC CANCER RESEARCH
Place of Publication: PHILADELPHIA
ISSN: 1557-3265
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CLASS-I ANTIGEN; B-CELLS; KIDNEY-TRANSPLANTATION; PROGNOSTIC-FACTOR; DOWN-REGULATION; IMMUNE CELLS; CARCINOMA; SURVIVAL; TUMOR; IMMUNOTHERAPYMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/67303

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