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

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, Timothy F. Cloughesy, Linda M. Liau () and Robert M. Prins ()
Additional contact information
Richard G. Everson: University of California Los Angeles
Willy Hugo: 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
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
Timothy F. Cloughesy: University of California Los Angeles
Linda M. Liau: University of California Los Angeles
Robert M. Prins: University of California Los Angeles

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-48073-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48073-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-48073-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().