ArticleJournal for immunotherapy of cancer2022
Unique characteristics of tertiary lymphoid structures in kidney clear cell carcinoma: prognostic outcome and comparison with bladder cancer.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Pooled it
- Tertiary lymphoid structures in cancer: their development, composition, clinical prognosis, and the drivers of the anti-tumor responses.Molecular biomedicine · 2026Review
- Review
- Pretreatment intratumoral mature TLSs in non-clear cell renal cell carcinoma are associated with response to immunotherapy rechallenge.Journal for immunotherapy of cancer · 2026Article
- The formation and function of tertiary lymphoid structures.Biomarker research · 2026Review
- Combining spatial and single-cell transcriptome data to analyze tertiary lymphoid structures in clear cell renal cell carcinoma reveals prognostic biomarkers.Journal of translational medicine · 2026Article
- Article
- Tertiary lymphoid structures in urothelial carcinoma: bridging spatial architecture with therapeutic vulnerability in the post-BCG era.Frontiers in immunology · 2026Review
- A Tertiary Lymphoid Structure-Derived Prognostic Signature Integrates Immune Microenvironment and Mutational Landscapes in Clear Cell Renal Cell Carcinoma.Human mutation · 2026Article
- Multiview deep-learning-enabled histopathology for prognostic and therapeutic stratification in stage II colorectal cancer: A retrospective multicenter study.PLoS medicine · 2026Observational
- The Emerging Role of B Cells and Tertiary Lymphoid Structures in Bladder Cancer.Current urology reports · 2025Review
- Targeting high endothelial venules: potential strategies for cancer treatment.Annals of medicine · 2025Review
- Impact of tertiary lymphoid structure scores and their stage of maturation on prognosis of colorectal cancer patients.Genes and immunity · 2025Article
- Role of tertiary lymphoid structures in the tumour microenvironment and immunotherapy response of renal cell carcinoma.Clinical and translational medicine · 2025Review
- Spatial and maturity heterogeneity of tertiary lymphoid structures shapes immune microenvironment and progression in prostate cancer.Journal of the National Cancer Center · 2025Article
- Immunological features of clear-cell renal-cell carcinoma and resistance to immune checkpoint inhibitors.Nature reviews. Nephrology · 2025Review
- The roles of tertiary lymphoid structures in orchestrating immune responses in peripheral organs.Inflammation and regeneration · 2025Review
- The Sunrise of Tertiary Lymphoid Structures in Cancer.Immunological reviews · 2025Review
- Tertiary Lymphoid Structures as Independent Predictors of Favorable Prognosis in Muscle-Invasive Bladder Cancer.Cancer medicine · 2025Article
- Prognostic impact and landscape of cellular CXCR5 chemokine receptor expression in clear-cell renal cell carcinoma.Cancer immunology, immunotherapy : CII · 2025Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe aims of this study were (1) to clarify the impact of tertiary lymphoid structure (TLS) status on the outcome and immunogenomic profile of human clear cell renal cell carcinoma (ccRCC) and (2) to determine phenotypic differences in TLSs between different types of genitourinary cancer, that is, urinary ccRCC and bladder cancer.
methodsWe performed a quantitative immunohistological analysis of ccRCC tissue microarrays and conducted integrated genome mutation analysis by next-generation sequencing and methylation array analysis. Since the tumor immune microenvironment of ccRCC often differs from that of other cancer types, we analyzed the phenotypic differences in TLSs between ccRCC and in-house bladder cancer specimens.
resultsVarying distribution patterns of TLSs were observed throughout ccRCC tumors, revealing that the presence of TLSs was related to poor prognosis. An analysis of genomic alterations based on TLS status in ccRCC revealed that alterations in the PI3K-mTOR pathway were highly prevalent in TLS-positive tumors. DNA methylation profiling also revealed distinct differences in methylation signatures among ccRCC samples with different TLS statuses. However, the TLS characteristics of ccRCC and bladder cancer markedly differed: TLSs had the exact opposite prognostic impact on bladder cancer as on ccRCC. The maturity and spatial distribution of TLSs were significantly different between the two cancer types; TLSs were more mature with follicle-like germinal center organization and likely to be observed inside the tumor in bladder cancer. Labeling for CD8, FOXP3, PD-1, and PD-L1 showed marked differences in the diversity of the immune microenvironment surrounding TLSs. The proportions of CD8-, FOXP3-, and PD-L1-positive cells were significantly higher in TLSs in bladder cancer than in TLSs in ccRCC; rather the proportion of PD-1-positive cells was significantly higher in TLSs in ccRCC than in TLSs in bladder cancer.
conclusionThe immunobiology of ccRCC is unique, and various cancerous phenomena conflict with that seen in other cancer types; therefore, comparing the TLS characteristics between ccRCC and bladder cancer may help reveal differences in the prognostic impact, maturity and spatial distribution of TLSs and in the immune environment surrounding TLSs between the two cancers.
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