Tumor-infiltrating B cells inhibit nasopharyngeal carcinoma metastasis

  • Cell Death Dis. 2026 Jun 2. doi: 10.1038/s41419-026-08940-6.
Jing Cai  #  1  2 ,  Xiangzhou Tan  #  1  2  3 ,  Xinglong Liu  1  2 ,  Juan Feng  1  2 ,  Xiangying Deng  4 ,  Lin Zhao  5  6
Affiliations
  • 1. Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, China.
  • 2. Hunan Clinical Medical Research Center for Cancer Pathogenic Genes Testing and Diagnosis, Changsha, China.
  • 3. Department of General Surgery, National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Central South University, Changsha, China.
  • 4. Institute of Medical Sciences, National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Central South University, Changsha, China.
  • 5. Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, China. [email protected].
  • 6. Hunan Clinical Medical Research Center for Cancer Pathogenic Genes Testing and Diagnosis, Changsha, China. [email protected].
  • # Contributed equally.
PMID: 42230534 DOI: 10.1038/s41419-026-08940-6
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.

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