The immune landscape of human thymic epithelial tumors

Zhongwei Xin, Mingjie Lin, Zhixing Hao, Di Chen, Yongyuan Chen, Xiaoke Chen, Xia Xu, Jinfan Li, Dang Wu, Ying Chai () and Pin Wu ()
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Zhongwei Xin: Zhejiang University
Mingjie Lin: Zhejiang University
Zhixing Hao: Zhejiang University
Di Chen: Zhejiang University
Yongyuan Chen: Zhejiang University
Xiaoke Chen: Zhejiang University
Xia Xu: Zhejiang University
Jinfan Li: Zhejiang University
Dang Wu: Zhejiang University
Ying Chai: Zhejiang University
Pin Wu: Zhejiang University

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Human thymic epithelial tumors (TET) are common malignancies in the anterior mediastinum with limited biological understanding. Here we show, by single cell analysis of the immune landscape, that the developmental pattern of intra-tumoral T-cells identify three types within TETs. We characterize the developmental alterations and TCR repertoires of tumor-infiltrating T cells in the context of the distinguishing epithelial tumor cell types. We demonstrate that a subset of tumor cells, featuring medullary thymic epithelial cell (TEC) phenotype and marked by KRT14/GNB3 expression, accumulate in type 1 TETs, while T-cell positive selection is inhibited. Type 2 TETs are dominated by CCL25+ cortical TEC-like cells that appear to promote T-cell positive selection. Interestingly, the CHI3L1+ medullary TEC-like cells that are the characteristic feature of type 3 TETs don’t seem to support T-cell development, however, they may induce a tissue-resident CD8+ T cell response. In summary, our work suggests that the molecular subtype of epithelial tumour cells in TETs determine their tumour immune microenvironment, thus GNB3 and CHI3L1 might predict the immunological behavior and hence prognosis of these tumours.

Date: 2022
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DOI: 10.1038/s41467-022-33170-7

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