{
  "abstract": "Background Perineural invasion (PNI) is a hallmark of malignancy in solid tumors, including oral squamous cell carcinoma (OSCC), and is closely associated with poor prognosis. Emerging evidence suggests a critical association between PNI and the tumor immune microenvironment (TME).Methods In this study, we used spatial transcriptomics, in vitro and in vivo experiments, and clinical specimen validation to systematically study the interplay between neural infiltration and immune modulation in OSCC.Results Our results suggest that intratumoral nerves may enhance the recruitment of regulatory T cells (Tregs) through C-C motif chemokine ligand 5 (CCL5)-mediated chemotaxis and further promote the acquisition of an immunosuppressive phenotype in Tregs by activating the RAMP1 signaling pathway. Through these coordinated mechanisms, neural components in the TME contribute to immune suppression and facilitate tumor progression. Therapeutically, both combination of CCL5 blockade with anti-CTLA-4 antibody and the combination of RAMP1 blockade with anti-PD-1 antibody exhibited significantly enhanced anti-tumor efficacy.Conclusions This study highlights a previously underappreciated neural-Treg axis in the TME and provides new insights into potential combinatorial strategies for cancer immunotherapy.",
  "authors": [
    {
      "affiliations": [
        "Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China",
        "College of Stomatology, Shanghai Jiao Tong University, Shanghai, China",
        "National Center for Stomatology",
        "National Clinical Research Center for Oral Diseases",
        "Shanghai Key Laboratory of Stomatology",
        "Shanghai Research Institute of Stomatology",
        "Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai, China"
      ],
      "name": "Kailiu Wu"
    },
    {
      "affiliations": [
        "Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China",
        "College of Stomatology, Shanghai Jiao Tong University, Shanghai, China",
        "National Center for Stomatology",
        "National Clinical Research Center for Oral Diseases",
        "Shanghai Key Laboratory of Stomatology",
        "Shanghai Research Institute of Stomatology",
        "Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai, China",
        "Digital Diagnosis and Treatment Innovation Center for Cancer, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China"
      ],
      "name": "Zhen Zhang"
    },
    {
      "affiliations": [
        "Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China",
        "College of Stomatology, Shanghai Jiao Tong University, Shanghai, China",
        "National Center for Stomatology",
        "National Clinical Research Center for Oral Diseases",
        "Shanghai Key Laboratory of Stomatology",
        "Shanghai Research Institute of Stomatology",
        "Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai, China"
      ],
      "name": "Xing Qin"
    },
    {
      "affiliations": [
        "Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China",
        "College of Stomatology, Shanghai Jiao Tong University, Shanghai, China",
        "National Center for Stomatology",
        "National Clinical Research Center for Oral Diseases",
        "Shanghai Key Laboratory of Stomatology",
        "Shanghai Research Institute of Stomatology",
        "Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai, China"
      ],
      "name": "Guanying Feng"
    },
    {
      "affiliations": [
        "Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China",
        "College of Stomatology, Shanghai Jiao Tong University, Shanghai, China",
        "National Center for Stomatology",
        "National Clinical Research Center for Oral Diseases",
        "Shanghai Key Laboratory of Stomatology",
        "Shanghai Research Institute of Stomatology",
        "Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai, China"
      ],
      "name": "Huasheng Li"
    },
    {
      "affiliations": [
        "Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China",
        "College of Stomatology, Shanghai Jiao Tong University, Shanghai, China",
        "National Center for Stomatology",
        "National Clinical Research Center for Oral Diseases",
        "Shanghai Key Laboratory of Stomatology",
        "Shanghai Research Institute of Stomatology",
        "Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai, China"
      ],
      "name": "Ruiyu Guo"
    },
    {
      "affiliations": [
        "Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China",
        "College of Stomatology, Shanghai Jiao Tong University, Shanghai, China",
        "National Center for Stomatology",
        "National Clinical Research Center for Oral Diseases",
        "Shanghai Key Laboratory of Stomatology",
        "Shanghai Research Institute of Stomatology",
        "Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai, China"
      ],
      "name": "Yuhua Hu"
    },
    {
      "affiliations": [
        "Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China",
        "College of Stomatology, Shanghai Jiao Tong University, Shanghai, China",
        "National Center for Stomatology",
        "National Clinical Research Center for Oral Diseases",
        "Shanghai Key Laboratory of Stomatology",
        "Shanghai Research Institute of Stomatology",
        "Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai, China"
      ],
      "name": "Yikang Ji"
    },
    {
      "affiliations": [
        "Department of Oral and Maxillofacial Surgery, Zhongshan Hospital, Fudan University, Shanghai, China",
        "Fengcheng Hospital of Fengxian District, Shanghai, China"
      ],
      "name": "Yang Wang"
    },
    {
      "affiliations": [
        "Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China",
        "College of Stomatology, Shanghai Jiao Tong University, Shanghai, China",
        "National Center for Stomatology",
        "National Clinical Research Center for Oral Diseases",
        "Shanghai Key Laboratory of Stomatology",
        "Shanghai Research Institute of Stomatology",
        "Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai, China"
      ],
      "name": "Ming Yan"
    },
    {
      "affiliations": [
        "Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China",
        "College of Stomatology, Shanghai Jiao Tong University, Shanghai, China",
        "National Center for Stomatology",
        "National Clinical Research Center for Oral Diseases",
        "Shanghai Key Laboratory of Stomatology",
        "Shanghai Research Institute of Stomatology",
        "Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai, China"
      ],
      "name": "Chenping Zhang"
    }
  ],
  "title": "Sensory neuron-derived CCL5 orchestrates an immunosuppressive niche via regulatory T cells to fuel head and neck tumor progression",
  "uid": "99ae495b-6e85-5686-b5ac-1072edc4c589"
}