{
  "abstract": "Background Bone metastasis (BM) drives therapeutic resistance and mortality in nasopharyngeal carcinoma (NPC). Tumor metabolites are crucial for NPC metastasis; however, the mechanisms by which these metabolites synergistically alter the immune microenvironment to promote BM remain unclear.Methods In this study, limited immune infiltration was observed in the NPC BM tumor microenvironment. Multiomics analysis has identified sphingosine kinase 1 (SPHK1) as a pivotal mediator driving BM and immune evasion in NPC, orchestrating the production of 1-phosphorylated sphingosine (S1P), which is critical for NPC pathogenesis.Results The aberrant buildup of lipid metabolites, along with immune microenvironment shifts, serves as a critical driver of NPC BM. Mechanistically, S1P enhanced osteoclast recruitment via S1PR3 binding and activated the Hippo pathway, worsening bone colonization and facilitating immune evasion by expanding the exhausted CD8 + T cell population.Conclusions The synergy between the SPHK1 inhibitor PF543 and anti-programmed cell death protein 1 therapy amplified treatment effectiveness beyond standalone approaches. Overall, the SPHK1/S1P pathway advances NPC growth and aids in suppressing immune defense. Regulation of lipid metabolism may be a therapeutic target against BM in NPC and may improve the effectiveness of immunotherapy.",
  "authors": [
    {
      "affiliations": [
        "Department of Radiation Oncology, Southern Medical University, Guangzhou, China"
      ],
      "name": "Yuanyuan Feng"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, Southern Medical University, Guangzhou, China"
      ],
      "name": "Hongmei Wang"
    },
    {
      "affiliations": [
        "First Clinical Medical College, Southern Medical University, Guangzhou, China"
      ],
      "name": "Ziyan Zhu"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, Southern Medical University, Guangzhou, China"
      ],
      "name": "Wenxiang Deng"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, Southern Medical University, Guangzhou, China"
      ],
      "name": "Xiaoyue He"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, Southern Medical University, Guangzhou, China"
      ],
      "name": "Yingying Yao"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, Southern Medical University, Guangzhou, China"
      ],
      "name": "Miao Song"
    },
    {
      "affiliations": [
        "Department of Otolaryngology, Head and Neck Surgery, Southern Medical University, Guangzhou, China"
      ],
      "name": "Xiaohong Peng"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, Southern Medical University, Guangzhou, China"
      ],
      "name": "Yanling Lin"
    },
    {
      "affiliations": [
        "Department of Radiation Oncology, Southern Medical University, Guangzhou, China"
      ],
      "name": "Longmei Cai"
    }
  ],
  "title": "Aberrant lipid metabolism reshapes the immune landscape in bone metastasis of nasopharyngeal carcinoma",
  "uid": "f07c2b6e-a250-58da-9da1-cdc2f2731139"
}