{
  "abstract": "Background The CpG/α-OX40 in situ vaccine strategy has shown efficacy in immune-hot tumors but remains ineffective in immune-cold tumors possibly due to immunosuppressive microenvironments characterized by myeloid-derived suppressor cells (MDSCs) infiltration and T cell exclusion. This study aims to investigate the antitumor effect of non-α-biased IL-2 combined with CpG/α-OX40 in mice.Methods Using 4T1 breast cancer and CT26 colon cancer models, we evaluated the antitumor effects of combining CpG/α-OX40 with a non-α-biased IL-2 variant via both intratumoral and subcutaneous routes. Tumor growth, lung metastasis, immune profile, and in vitro function analysis were assessed through flow cytometry, transcriptomic analysis, and T cell suppression assays.Results The combination therapy significantly inhibited primary and distant tumor growth and reduced lung metastasis in 4T1 models. Subcutaneous administration induced complete tumor regression in 55% (5/9) of CT26-tumor-bearing mice and conferred durable tumor-specific memory. Mechanistically, the treatment enhanced CD8 + T cell activation, metabolic reprogramming, and IFN-γ production, while suppressing MDSC expansion and immunosuppressive function.Conclusions These findings demonstrate that non-α-biased IL-2 synergizes with CpG/α-OX40 to overcome microenvironmental immunosuppression and achieve systemic antitumor immunity via a subcutaneous route, offering a translatable combinatorial strategy for immune-cold tumors.",
  "authors": [
    {
      "affiliations": [
        "Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China"
      ],
      "name": "Kejie Huang"
    },
    {
      "affiliations": [
        "Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China",
        "Department of Ultrasound Medicine, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China"
      ],
      "name": "Xiaobo Ding"
    },
    {
      "affiliations": [
        "Department of Oncology, Cangnan Hospital Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang, China"
      ],
      "name": "Xuehuan Wen"
    },
    {
      "affiliations": [
        "Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China"
      ],
      "name": "Chaoming Huang"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China"
      ],
      "name": "Yan Chen"
    },
    {
      "affiliations": [
        "Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China"
      ],
      "name": "Xujie Zhou"
    },
    {
      "affiliations": [
        "Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China"
      ],
      "name": "Leying Zhou"
    },
    {
      "affiliations": [
        "Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China"
      ],
      "name": "Yi He"
    },
    {
      "affiliations": [
        "Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China"
      ],
      "name": "Zhixiang Bai"
    },
    {
      "affiliations": [
        "Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China"
      ],
      "name": "Chunhong Zhang"
    },
    {
      "affiliations": [
        "Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China"
      ],
      "name": "Yi Jin"
    },
    {
      "affiliations": [
        "Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China"
      ],
      "name": "Jianmin Li"
    },
    {
      "affiliations": [
        "Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China"
      ],
      "name": "Zhenghua Fei"
    },
    {
      "affiliations": [
        "Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China"
      ],
      "name": "Wenfeng Li"
    },
    {
      "affiliations": [
        "Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China"
      ],
      "name": "Chen Chen"
    }
  ],
  "title": "Non-α-biased IL-2 enhances both intratumoral and subcutaneous CpG/α-OX40 therapy, unleashing systemic antitumor immunity in mice",
  "uid": "d0cd7d9f-e2f3-5c51-a1f3-16242b2438eb"
}