{
  "abstract": "Background Identifying effective therapeutic drugs in the intricate tumor microenvironment (TME) is challenging, further complicated by the lack of a systematic framework for analyzing TME perturbations in response to therapeutic interventions.Methods To address this, we established the single-cell RNA sequencing repository of immunomodulatory drugs resource and used the L1000 platform for unbiased screening of 739 immune-modulating compounds across various cancers.Results Drug responses in mouse model revealed 12 distinct meta-programs associated with TME remodeling, enriched in biological processes such as antigen presentation, tissue repair, and salt stress response. Notably, myeloid-derived suppressor cells were markedly reduced in responsive TMEs compared with other cell types, underscoring their key immunosuppressive role. We developed an MP scoring algorithm to quantify TME responsiveness, which successfully identified allopurinol—a gout medication—as a potent enhancer of anti-programmed cell death protein-1 therapy. This combination led to significant tumor-free outcomes (4/6) in vivo.Conclusions This work provides a robust framework for assessing TME remodeling that uncovers genes and compounds that significantly modulate immunotherapeutic efficacy.",
  "authors": [
    {
      "affiliations": [
        "Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, College of Pharmacy, Chongqing Medical University, Chongqing, China",
        "Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China"
      ],
      "name": "Ziruoyu Wang"
    },
    {
      "affiliations": [
        "Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, College of Pharmacy, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Junchi Hu"
    },
    {
      "affiliations": [
        "Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, College of Pharmacy, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Kailu Liu"
    },
    {
      "affiliations": [
        "Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, College of Pharmacy, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Jie Xu"
    },
    {
      "affiliations": [
        "Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, College of Pharmacy, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Jiao Li"
    },
    {
      "affiliations": [
        "Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, College of Pharmacy, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Yihang Liu"
    },
    {
      "affiliations": [
        "Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, College of Pharmacy, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Qinfeng Ma"
    },
    {
      "affiliations": [
        "Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China"
      ],
      "name": "Yu Dong"
    },
    {
      "affiliations": [
        "Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, College of Pharmacy, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Yunmei Zhu"
    },
    {
      "affiliations": [
        "Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, College of Pharmacy, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Kai Zhang"
    },
    {
      "affiliations": [
        "College of Basic Medicine, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Dexin Wang"
    },
    {
      "affiliations": [
        "Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, College of Pharmacy, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Xiaobo Wang"
    },
    {
      "affiliations": [
        "Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, College of Pharmacy, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Shuai Wang"
    },
    {
      "affiliations": [
        "Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, College of Pharmacy, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Jianbo Pan"
    },
    {
      "affiliations": [
        "Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China"
      ],
      "name": "Shuai Jiang"
    },
    {
      "affiliations": [
        "Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, College of Pharmacy, Chongqing Medical University, Chongqing, China"
      ],
      "name": "Jiaxue Wu"
    },
    {
      "affiliations": [
        "Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China"
      ],
      "name": "Wei Jiang"
    },
    {
      "affiliations": [
        "Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China"
      ],
      "name": "Ling Zhang"
    },
    {
      "affiliations": [
        "Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, College of Pharmacy, Chongqing Medical University, Chongqing, China",
        "Basic Medicine Research and Innovation Center for Novel Target and Therapeutic Intervention, Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China"
      ],
      "name": "Yongjun Dang"
    }
  ],
  "title": "Single-cell-based identification of drug synergy with immunotherapy via tumor microenvironment remodeling",
  "uid": "87d5e35f-aeb6-586d-8fca-a1ad2f97a0f8"
}