Abstract Nasopharyngeal carcinoma (NPC) in advanced stages often has a poor prognosis due to distant metastasis, yet the distribution characteristics and anti-metastatic mechanisms of tumor-infiltrating B cells (TIL-B) remain unclear. In this study, single-cell RNA sequencing combined with multiplex immunofluorescence revealed that B cells were highly enriched in non-metastatic NPC and formed complete tertiary lymphoid structures (TLS), whereas TLS was absent in metastatic NPC. Functional assays in vitro and in vivo showed that TIL-B and their conditioned medium significantly inhibited NPC cell proliferation, migration, and epithelial-mesenchymal transition (EMT), while inducing apoptosis; in humanized mouse models, TIL-B suppressed subcutaneous tumor growth and lung metastasis, whereas B cell depletion accelerated tumor progression. Mechanistically, TIL-B secreted IL-12, IFN-γ, TNF-α, and CXCL13. Among them, IL-12 upregulated E-cadherin and downregulated N-cadherin and Vimentin, thereby blocking EMT and inhibiting vasculogenic mimicry (VM); CXCL13 may promote TLS formation and enhance local immune responses. Through the dual pathways of “ IL-12-EMT/VM inhibition” and “CXCL13-TLS construction,” TIL-B cooperatively restrains tumor invasion and metastasis, building a multidimensional immune defense system. This study demonstrates that TIL-B play an important regulatory role in anti-tumor immunity in NPC and suggests their therapeutic potential, providing a rationale for the development of B cell-based or TLS-targeted immunotherapeutic strategies.
Cai et al. (Tue,) studied this question.