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

Feb 11, 2025Cancer immunology, immunotherapy : CII

Differences in development and location of immune cell clusters in head and neck cancer linked to tumor defense and patient outcomes

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

In a study of 260 patients with head and neck squamous cell carcinoma, mature intratumor (Intra-TLSs) are associated with improved 5-year survival rates.

Mature Intra-TLSs contain increased densities of memory B cells, plasma cells, and CD4T cells.
Early TLSs (E-TLSs) show high levels of endothelial cells, fibroblasts, and regulatory T cells, which may promote tumor growth.
Mature Intra-TLSs exhibit heightened expression of genes related to B-cell activity and immune responses.
Mature Peri-TLSs, characterized by endothelial cell enrichment, may facilitate tumor progression and immune evasion.
A novel TLS scoring system was developed to predict survival outcomes based on TLS maturity and distribution.

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The influence of (TLSs) on disease progression and the response to 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 CD4T 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. +

Key numbers

better than 50%

5-year survival rate for mature Intra-

Survival outcomes based on TLS maturity and spatial distribution.

260

260 patients analyzed

Total number of HNSCC patients included in the study.

four

TLS scoring system categories

Number of distinct immune subtypes defined by the TLS scoring system.

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

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