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Association of CCL21+ CAFs with B-cell recruitment and TLS maturation in penile squamous cell carcinoma - PubMed

6 hours ago
  • #Cancer-associated fibroblasts
  • #Tertiary lymphoid structures
  • #Penile cancer
  • Penile squamous cell carcinoma (PSCC) is an aggressive malignancy with poor prognosis and limited treatment options.
  • Tertiary lymphoid structures (TLSs) support antitumour immunity, but their maturation and stromal determinants in PSCC are unclear.
  • Study used H&E staining, mIHC, spatial transcriptomics, scRNA-seq, and bulk RNA-seq to analyze TLS maturity and associated stromal-immune features in PSCC.
  • Mature TLSs (mTLSs) correlated with improved survival and were identified using a germinal centre-like signature.
  • CCL21+ cancer-associated fibroblasts (CAFs) were enriched in mTLSs, spatially concentrated near B-cell-rich areas.
  • The CCL21-CCR7 axis was linked to B-cell chemotaxis, activation, and germinal centre-like features.
  • Higher CCL21 expression, CCL21+ CAF signature scores, and CCL21-CCR7 signatures in B cells were associated with better outcomes.
  • CCL21+ CAFs or CCL21 may serve as prognostic biomarkers and potential therapeutic targets for TLS modulation in PSCC.