Distinct maturity and spatial distribution of tertiary lymphoid structures in head and neck squamous cell carcinoma: implications for tumor immunity and clinical outcomes.

IF 4.6 2区 医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2025-02-11 DOI:10.1007/s00262-025-03952-1
Shuai Xu, Chao Han, Jian Zhou, Di Yang, Hui Dong, Yiwei Zhang, Tingting Zhao, Yi Tian, Yuzhang Wu
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Abstract

The influence of tertiary lymphoid structures (TLSs) on disease progression and the response to immunotherapy in head and neck squamous cell carcinoma (HNSCC) is well established, yet the heterogeneity among these structures remains largely unexplored. We utilized digital spatial profiling technology to perform in situ transcriptomic sequencing of TLSs across varying levels of maturation and distinct tumor regions within HNSCC. We assessed the prognostic significance of TLS maturation and spatial distribution in 260 patients with HNSCC through hematoxylin and eosin staining and multiplex immunohistochemistry. Furthermore, we established a TLS scoring system to predict survival in patients with HNSCC. Our study revealed that mature TLSs in the intratumor region (Intra-TLSs) of HNSCC, enriched with memory B cells, plasma cells, and CD4+ T cells, presented increased B-cell activity gene expression. Conversely, early TLSs (E-TLSs), abundant in endothelial cells, fibroblasts, and regulatory T cells, express epithelial‒mesenchymal transition (EMT)-related genes, potentially fostering tumor growth. Compared with mature TLSs within the peritumoral region (Peri-TLSs), mature Intra-TLSs have greater memory B-cell and macrophage densities and upregulate genes involved in B-cell receptor signaling and immune effector processes. Mature Peri-TLSs, characterized by endothelial cell enrichment and EMT receptor interaction genes, may contribute to tumor progression and immune evasion. Patients with mature Intra-TLSs or invasive margin TLSs (Invas-TLSs) have improved 5-year survival, whereas those with mature Peri-TLSs have poorer prognoses. By integrating TLS maturity and distribution in HNSCC, we developed a TLS scoring system to guide personalized treatments, which is crucial for predicting outcomes.

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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
期刊最新文献
PD1+ Treg cell remodeling promotes immune homeostasis within peripheral blood and tumor microenvironment after microparticles-transarterial chemoembolization in hepatocellular carcinoma. Characterization of canine tumor-infiltrating leukocyte transcriptomic signatures reveals conserved expression patterns with human osteosarcoma. Chidamide functions as a VISTA/PSGL-1 blocker for cancer immunotherapy. Distinct maturity and spatial distribution of tertiary lymphoid structures in head and neck squamous cell carcinoma: implications for tumor immunity and clinical outcomes. Neutrophil-induced pyroptosis promotes survival in patients with hepatoblastoma.
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