| Autor: |
Hans A. Schlößer, Dirk L. Stippel, Heike Löser, Cornelia Mauch, Christine Kurschat, Christiane J. Bruns, Alexander Quaas, Michael S. von Bergwelt-Baildon, Peter Zentis, Ella Preugszat, Kerstin Wennhold, Maria A. Garcia-Marquez, Jonas Lehmann, Martin Thelen, Claire Aguilar, Oana-Diana Persa, Simon Schran, Rabi R. Datta |
| Rok vydání: |
2023 |
| Popis: |
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 immunosurveillance is assumed as underlying mechanism. This study aims to elucidate transplant-related changes in the tumor immune microenvironment (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+ T cells than for CD3+ 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 immunosuppression on the TME and supports impaired cancer immunosurveillance as important cause of post-transplant cancer. Modern immunosuppressive protocols and cancer therapies should consider the distinct immune microenvironment of post-transplant malignancies. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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