{
  "abstract": "Background Neoantigen-specific tumor-infiltrating lymphocytes (TILs) have the ability to mediate responses in patients with metastatic epithelial cancers. While some identified factors are associated with response, there is a need for ways to determine which patients will benefit from adoptive cell therapy with TIL. Patient-derived tumor organoids (PDTO) retain the genetic makeup of the tumor from which they are derived, and are a useful tool in personalized medicine to test the effectiveness of anticancer therapies.Methods Tumor organoids were grown from patients with metastatic epithelial cancers treated on a TIL protocol. TIL recognition of autologous PDTO by enzyme-linked immunosorbent spot assays and 4–1BB upregulation, as well as objective Response Evaluation Criteria in Solid Tumors (RECIST) responses to treatment, were measured in a cohort of treated patients. The most common histologies were colorectal (20 patients, 67%), pancreatic (4 patients, 13%), and breast (2 patients, 7%) cancer.Results Recognition of PDTO was driven by major histocompatibility complex (MHC) class I-restricted reactivity and upregulation of MHC in response to interferon-γ was not associated with response. There were no responders in the 9 patients who lacked PDTO recognition on their initial TIL screening compared with seven responses in 18 patients with initial reactivity (p=0.059). After TIL were selected and expanded for administration, 15 infusion products showed organoid recognition, with 8 of these patients achieving objective responses (53%), while only 1 of 15 patients without organoid recognition responded (7%; p=0.014).Conclusions TIL reactivity against autologous tumor organoid appears to be associated with objective clinical response in patients with metastatic epithelial cancers.",
  "authors": [
    {
      "affiliations": [
        "Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA",
        "Surgery, Yale School of Medicine, New Haven, Connecticut, USA"
      ],
      "name": "Alexandra M Gustafson"
    },
    {
      "affiliations": [
        "Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"
      ],
      "name": "Aarushi Bhasin"
    },
    {
      "affiliations": [
        "Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA",
        "Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland, USA"
      ],
      "name": "Billel Gasmi"
    },
    {
      "affiliations": [
        "Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"
      ],
      "name": "Brian D Bui"
    },
    {
      "affiliations": [
        "Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"
      ],
      "name": "Catherine Marie Ade"
    },
    {
      "affiliations": [
        "Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"
      ],
      "name": "Ken-ichi Hanada"
    },
    {
      "affiliations": [
        "Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"
      ],
      "name": "Hyunmi K Halas"
    },
    {
      "affiliations": [
        "Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"
      ],
      "name": "Jared J Gartner"
    },
    {
      "affiliations": [
        "Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"
      ],
      "name": "Todd D Prickett"
    },
    {
      "affiliations": [
        "Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"
      ],
      "name": "Jon Salazar"
    },
    {
      "affiliations": [
        "Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"
      ],
      "name": "Maria R Parkhust"
    },
    {
      "affiliations": [
        "Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"
      ],
      "name": "Paul Robbins"
    },
    {
      "affiliations": [
        "Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"
      ],
      "name": "Nicholas D Klemen"
    },
    {
      "affiliations": [
        "Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"
      ],
      "name": "Mei Li Kwong"
    },
    {
      "affiliations": [
        "Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"
      ],
      "name": "Stephanie L Goff"
    },
    {
      "affiliations": [
        "Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"
      ],
      "name": "Steven A Rosenberg"
    },
    {
      "affiliations": [
        "Surgery Branch, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, USA"
      ],
      "name": "James C Yang"
    }
  ],
  "title": "Correlation between recognition of autologous tumor organoids by tumor-infiltrating lymphocytes from metastatic epithelial cancers and clinical response",
  "uid": "1fb9a2f0-2107-5631-b47f-1f6bd853344f"
}