免疫监视
免疫抑制
肿瘤微环境
免疫系统
癌症
CD8型
免疫学
医学
病理
生物
作者
Rabi R Datta,Simon Schran,Oana-Diana Persa,Claire Aguilar,Martin Thelen,Jonas Lehmann,Maria A Garcia-Marquez,Kerstin Wennhold,Ella Preugszat,Peter Zentis,Michael S von Bergwelt-Baildon,Alexander Quaas,Christiane J Bruns,Christine Kurschat,Cornelia Mauch,Heike Löser,Dirk L. Stippel,Hans A. Schlößer
出处
期刊:Clinical Cancer Research
[American Association for Cancer Research]
日期:2022-02-09
卷期号:: clincanres.3746.2021-clincanres.3746.2021
标识
DOI:10.1158/1078-0432.ccr-21-3746
摘要
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.Data from 123 organ transplant recipients (kidney, heart, lung, and liver) were compared to 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 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.We found a remarkably reduced immune infiltrate in the center tumor regions (CT) 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 tertiary lymphoid structures 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.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.
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