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TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial

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  • Richard G. Everson

    (University of California Los Angeles
    University of California Los Angeles)

  • Willy Hugo

    (University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles)

  • Lu Sun

    (University of California Los Angeles)

  • Joseph Antonios

    (University of California Los Angeles)

  • Alexander Lee

    (University of California Los Angeles
    University of California Los Angeles)

  • Lizhong Ding

    (University of California Los Angeles)

  • Melissa Bu

    (University of California Los Angeles)

  • Sara Khattab

    (University of California Los Angeles)

  • Carolina Chavez

    (University of California Los Angeles)

  • Emma Billingslea-Yoon

    (University of California Los Angeles)

  • Andres Salazar

    (Inc.)

  • Benjamin M. Ellingson

    (University of California Los Angeles
    University of California Los Angeles)

  • Timothy F. Cloughesy

    (University of California Los Angeles
    University of California Los Angeles)

  • Linda M. Liau

    (University of California Los Angeles
    University of California Los Angeles)

  • Robert M. Prins

    (University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles
    University of California Los Angeles)

Abstract

In this randomized phase II clinical trial, we evaluated the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to autologous tumor lysate-pulsed dendritic cell (ATL-DC) vaccination in patients with newly-diagnosed or recurrent WHO Grade III-IV malignant gliomas. The primary endpoints were to assess the most effective combination of vaccine and adjuvant in order to enhance the immune potency, along with safety. The combination of ATL-DC vaccination and TLR agonist was safe and found to enhance systemic immune responses, as indicated by increased interferon gene expression and changes in immune cell activation. Specifically, PD-1 expression increases on CD4+ T-cells, while CD38 and CD39 expression are reduced on CD8+ T cells, alongside an increase in monocytes. Poly-ICLC treatment amplifies the induction of interferon-induced genes in monocytes and T lymphocytes. Patients that exhibit higher interferon response gene expression demonstrate prolonged survival and delayed disease progression. These findings suggest that combining ATL-DC with poly-ICLC can induce a polarized interferon response in circulating monocytes and CD8+ T cells, which may represent an important blood biomarker for immunotherapy in this patient population.Trial Registration: ClinicalTrials.gov Identifier: NCT01204684.

Suggested Citation

  • Richard G. Everson & Willy Hugo & Lu Sun & Joseph Antonios & Alexander Lee & Lizhong Ding & Melissa Bu & Sara Khattab & Carolina Chavez & Emma Billingslea-Yoon & Andres Salazar & Benjamin M. Ellingson, 2024. "TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48073-y
    DOI: 10.1038/s41467-024-48073-y
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    References listed on IDEAS

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    1. Ruslan Medzhitov, 2007. "Recognition of microorganisms and activation of the immune response," Nature, Nature, vol. 449(7164), pages 819-826, October.
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