Prognostic value, DNA variation and immunologic features of a tertiary lymphoid structure-related chemokine signature in clear cell renal cell carcinoma
- 19.01.2022
- Original Article
Erschienen in:
- Verfasst von
- Wenhao Xu
- Chunguang Ma
- Wangrui Liu
- Aihetaimujiang Anwaier
- Xi Tian
- Guohai Shi
- Yuanyuan Qu
- Shiyin Wei
- Hailiang Zhang
- Dingwei Ye
- Erschienen in
- Cancer Immunology, Immunotherapy | Ausgabe 8/2022
Abstract
Background
The tumor microenvironment (TME) and tertiary lymphoid structures (TLS) affect the occurrence and development of cancers. How the immune contexture interacts with the phenotype of clear cell renal cell carcinoma (ccRCC) remains unclear.
Methods
We identified and evaluated TLS clusters in ccRCC using machine learning algorithms and the 12-chemokine gene signature for TLS. Analyses for functional enrichment, DNA variation, immune cell distribution, association with independent clinicopathological features and predictive value of CXCL13 in ccRCC were performed.
Results
We found a prominently enrichment of the 12-chemokine gene signature for TLS in patients with ccRCC compared with other types of renal cell carcinoma. We identified a prognostic value of CCL4, CCL5, CCL8, CCL19 and CXCL13 expression in ccRCC. DNA deletion of the TLS gene signature significantly predicted poor outcome in ccRCC compared with amplification and wild-type gene signature. We established TLS clusters (C1–4) and observed distinct differences in survival, stem cell-like characteristics, immune cell distribution, response to immunotherapies and VEGF-targeted therapies among the clusters. We found that elevated CXCL13 expression significantly predicted aggressive progression and poor prognosis in 232 patients with ccRCC in a real-world validation cohort.
Conclusion
This study described a 12-chemokine gene signature for TLS in ccRCC and established TLS clusters that reflected different TME immune status and corresponded to prognosis of ccRCC. We confirmed the dense presence of TILs aggregation and TLS in ccRCC and demonstrated an oncogenic role of CXCL13 expression of ccRCC, which help develop immunotherapies and provide novel insights on the long-term management of ccRCC.
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- Titel
- Prognostic value, DNA variation and immunologic features of a tertiary lymphoid structure-related chemokine signature in clear cell renal cell carcinoma
- Verfasst von
-
Wenhao Xu
Chunguang Ma
Wangrui Liu
Aihetaimujiang Anwaier
Xi Tian
Guohai Shi
Yuanyuan Qu
Shiyin Wei
Hailiang Zhang
Dingwei Ye
- Publikationsdatum
- 19.01.2022
- Verlag
- Springer Berlin Heidelberg
- Erschienen in
-
Cancer Immunology, Immunotherapy / Ausgabe 8/2022
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851 - DOI
- https://doi.org/10.1007/s00262-021-03123-y
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