{
  "abstract": "The ability to interrogate changes within the tumor microenvironment (TME) before, during and following therapeutic intervention could yield important understanding of treatment response and causes for disease progression. Yet, the role of investigational tissue analysis faces key challenges in the clinical setting and the value of integrating longitudinal biopsies with emerging multimodal molecular analyses (“Multi-omics”) remains to be defined. In this study, we conducted a multicenter phase 2 clinical trial examining the effect of a novel cytotoxic T-lymphocyte-associated protein 4/programmed death-ligand 1 bispecific antibody in combination with a dual-epitope blocking anti-human epidermal growth factor receptor 2 antibody in treatment-resistant metastatic breast cancer. We performed longitudinal sampling of patient tumor tissues before and following treatment. Single-cell RNA and T cell receptor sequencing from 334,183 cells from site-matched tumors reveals significant temporal shift of various immune cell populations and phenotypes within the TME associated with treatment responses. Conversely, regulatory T cells were activated while effector T cells, natural killer cells, and dendritic cells were significantly depleted in non-responding tumors. Taken together, these results support that longitudinal analysis of TME to generate multiomics data that can lead to rich insight into disease process and to provide clinical value in evaluating treatment responses. Trial registration number NCT04521179.",
  "authors": [
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China",
        "Center for Precision Medicine, Shenshan Central Hospital, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Shenwei, People's Republic of China"
      ],
      "name": "Jian-You Liao"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China"
      ],
      "name": "Jien Wang"
    },
    {
      "affiliations": [
        "Department of Breast and Thyroid Surgery, Naval Military Medical University, Shanghai, China"
      ],
      "name": "Hengyu Li"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China"
      ],
      "name": "Zhijun Liu"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China"
      ],
      "name": "Zhenluan Tian"
    },
    {
      "affiliations": [
        "Department of Breast Surgery, Fujian Cancer Hospital, Fuzhou, China",
        "Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, China"
      ],
      "name": "Xinying Lv"
    },
    {
      "affiliations": [
        "Jiangsu Alphamab Biopharmaceuticals Co.,Ltd, Suzhou, People's Republic of China"
      ],
      "name": "Jianjian Peng"
    },
    {
      "affiliations": [
        "Department of Breast Surgery, Fujian Cancer Hospital, Fuzhou, China",
        "Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, China"
      ],
      "name": "Chuangui Song"
    },
    {
      "affiliations": [
        "Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China"
      ],
      "name": "Jieqiong Liu"
    }
  ],
  "title": "Longitudinal tissue analysis reveals microenvironmental changes correlate with combined immunotherapy and targeted therapy response in metastatic breast cancer",
  "uid": "b0e52fc6-9a39-5910-9aad-6ca2e02ab011"
}