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Title:
An ex vivo tumor fragment platform to dissect response to PD-1 blockade in cancer | Nature Medicine
Description:
Inhibitors of the PD-1–PD-L1 axis have been approved as therapy for many human cancers. In spite of the evidence for their widespread clinical activity, little is known about the immunological alterations that occur in human cancer tissue after PD-1 blockade. We developed and employed a patient-derived tumor fragment platform to dissect the early immunological response of human tumor tissue to ex vivo PD-1 blockade. We observed that the capacity of immune cells to be reactivated ex vivo was predictive of clinical response, and perturbation analyses identified tumor-resident T cells as a key component of this immunological response. In addition, through combined analysis of baseline properties and immune response capacity, we identified a new subgroup of infiltrated tumors that lacks the capacity to respond to PD-1 blockade. Finally, the baseline presence of tertiary lymphoid structures and their components correlated with the capacity of cancers to undergo intratumoral immune cell reactivation. An ex vivo platform of patient-derived tumor fragments enables the assessment of intratumoral immune reactivation after PD-1 blockade that is predictive of clinical outcomes in patients with cancer.
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headline:An ex vivo tumor fragment platform to dissect response to PD-1 blockade in cancer
description:Inhibitors of the PD-1âPD-L1 axis have been approved as therapy for many human cancers. In spite of the evidence for their widespread clinical activity, little is known about the immunological alterations that occur in human cancer tissue after PD-1 blockade. We developed and employed a patient-derived tumor fragment platform to dissect the early immunological response of human tumor tissue to ex vivo PD-1 blockade. We observed that the capacity of immune cells to be reactivated ex vivo was predictive of clinical response, and perturbation analyses identified tumor-resident T cells as a key component of this immunological response. In addition, through combined analysis of baseline properties and immune response capacity, we identified a new subgroup of infiltrated tumors that lacks the capacity to respond to PD-1 blockade. Finally, the baseline presence of tertiary lymphoid structures and their components correlated with the capacity of cancers to undergo intratumoral immune cell reactivation. An ex vivo platform of patient-derived tumor fragments enables the assessment of intratumoral immune reactivation after PD-1 blockade that is predictive of clinical outcomes in patients with cancer.
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url:http://orcid.org/0000-0003-0517-8804
affiliation:
name:Oncode Institute, Netherlands Cancer Institute
address:
name:Division of Molecular Oncology & Immunology, Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands
type:PostalAddress
type:Organization
name:Daniela S. Thommen
url:http://orcid.org/0000-0002-7431-2854
affiliation:
name:Netherlands Cancer Institute
address:
name:Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Division of Molecular Oncology & Immunology, Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands
name:Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands
name:Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands
name:Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands
name:Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands
name:Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands
name:Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands
name:Department of Molecular Cell Biology and Immunology, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
name:Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands
name:Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands
name:Department of Biomedicine, University Hospital Basel, Basel, Switzerland
name:Department of Biomedicine, University Hospital Basel, Basel, Switzerland
name:Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands
name:Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
name:Department of Surgery, Netherlands Cancer Institute, Amsterdam, the Netherlands
name:Department of Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands
name:Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands
name:Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands
name:Division of Molecular Oncology & Immunology, Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands
name:Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, the Netherlands
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