{
  "abstract": "Background Areca nut is the fourth most addictive substance worldwide and is a known Group 1 carcinogen. Chronic areca nut chewing has been strongly associated with the development of oral squamous cell carcinoma (OSCC), although the underlying carcinogenic mechanisms remain unclear.Methods Employing spatial multiomics technology, we recently mapped the immune microenvironment of areca nut-associated OSCC and identified a marked upregulation of the immune checkpoint molecule CD155 in these tumors. Further quantitative reverse transcription-PCR, western blotting, immunofluorescence, animal experiments, etc, explored and verified the reasons for the upregulation of CD155 caused by arecoline and the results of immune escape in OSCC.Results The investigation revealed that arecoline, a bioactive component of areca nut, induces CD155 expression in OSCC cells. Through interaction with its receptor, TIGIT, CD155 suppresses CD8 + T cell function and activity, facilitating immune evasion in OSCC. Mechanistically, arecoline upregulates CD155 via activation of muscarinic acetylcholine receptors on the surface of OSCC cells, leading to RhoA-mediated inhibition of YAP phosphorylation. This promotes YAP nuclear translocation and phase separation, driving CD155 transcription. In both in vitro and in vivo models, blockade of the CD155–TIGIT signaling axis significantly enhanced the efficacy of immunotherapy in OSCC.Conclusion This study unveils a novel mechanism by which arecoline promotes immune evasion in OSCC and highlights promising immune therapeutic targets and strategies for the treatment of areca nut-associated OSCC.",
  "authors": [
    {
      "affiliations": [
        "NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Xiangya School of Basic Medicine Sciences, Central South University, Changsha, Hunan, China",
        "Furong Laboratory, Changsha, Hunan, China"
      ],
      "name": "Qian Wang"
    },
    {
      "affiliations": [
        "NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Xiangya School of Basic Medicine Sciences, Central South University, Changsha, Hunan, China",
        "Furong Laboratory, Changsha, Hunan, China"
      ],
      "name": "Yi Meng"
    },
    {
      "affiliations": [
        "NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Xiangya School of Basic Medicine Sciences, Central South University, Changsha, Hunan, China",
        "Furong Laboratory, Changsha, Hunan, China"
      ],
      "name": "Yuhang Liu"
    },
    {
      "affiliations": [
        "Department of Oral Medicine, Center of Stomatology, Xiangya Hospital Central South University, Changsha, Hunan, China"
      ],
      "name": "Shanshan Zhang"
    },
    {
      "affiliations": [
        "Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Xiangya School of Basic Medicine Sciences, Central South University, Changsha, Hunan, China"
      ],
      "name": "Yian Wang"
    },
    {
      "affiliations": [
        "NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China"
      ],
      "name": "Pan Chen"
    },
    {
      "affiliations": [
        "Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Xiangya School of Basic Medicine Sciences, Central South University, Changsha, Hunan, China",
        "Furong Laboratory, Changsha, Hunan, China"
      ],
      "name": "Bo Xiang"
    },
    {
      "affiliations": [
        "Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Xiangya School of Basic Medicine Sciences, Central South University, Changsha, Hunan, China",
        "Furong Laboratory, Changsha, Hunan, China"
      ],
      "name": "Ming Zhou"
    },
    {
      "affiliations": [
        "Department of Oral and Maxillofacial Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China"
      ],
      "name": "Zhaojian Gong"
    },
    {
      "affiliations": [
        "NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Xiangya School of Basic Medicine Sciences, Central South University, Changsha, Hunan, China",
        "Furong Laboratory, Changsha, Hunan, China"
      ],
      "name": "Zhaoyang Zeng"
    },
    {
      "affiliations": [
        "Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Xiangya School of Basic Medicine Sciences, Central South University, Changsha, Hunan, China"
      ],
      "name": "Junshang Ge"
    },
    {
      "affiliations": [
        "NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and Xiangya School of Basic Medicine Sciences, Central South University, Changsha, Hunan, China",
        "Furong Laboratory, Changsha, Hunan, China"
      ],
      "name": "Wei Xiong"
    }
  ],
  "title": "Arecoline upregulates CD155 expression to facilitate immune evasion in oral squamous cell carcinoma",
  "uid": "18d31df0-dab5-5240-8719-c5a53dd73b73"
}