Single-cell transcriptomic analysis reveals dynamic changes in the microenvironment of nasopharyngeal carcinoma during metastatic progression.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated malignancy with a high propensity for distant metastasis and hence conferring the poorest prognosis. Treatment failure remains, despite improvement in primary tumor outcomes by advances in local control, which is predominantly attributable to the distant metastasis. So far, there is still a poor understanding of cellular and immunological mechanisms underlying NPC liver metastasis (NPCLM). Here, this study was performed to delineate dynamic changes in the tumor microenvironment during metastatic progression through the construction of a comprehensive single-cell transcriptomic atlas of primary NPC and NPCLM. Our analysis observed marked remodeling of immune cell composition and function between primary and metastatic sites. Furthermore, we identified distinct T and B cell subsets, characterized by functional alterations in T cells and the acquisition of stem-like properties in regulatory T cells during metastasis. Notably, unfavorable clinical outcomes were found to be related to the interaction between enhanced macrophage migration inhibitory factor (MIF)-mediated tumor and T cells. Among T cell populations, a CD4⁺ T cell subset expressing CXCL13 was identified to be preferentially enriched in liver metastases, which promoted the recruitment and activation of B cells within the metastatic niche. Additionally, the loss of the C2_Bn_IGHM B cell signature might imply metastatic progression and reduced overall survival. In summary, our study characterizes the immune landscape of NPC metastasis, with the profiling of critical immune cell subsets and intercellular interactions that may drive NPCLM and influence patient prognosis, offering potential targets for therapeutic intervention.