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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1433119
This article is part of the Research Topic Plasmacytoid Dendritic Cell and Cancer, Exploring Missing Links for Translation to Real World View all articles

Human CD34 + -derived plasmacytoid dendritic cells as surrogates for primary pDCs and potential cancer immunotherapy

Provisionally accepted
Giovanna Fiore Giovanna Fiore 1Wolfgang Weckwarth Wolfgang Weckwarth 1Kerstin Paetzold Kerstin Paetzold 1Llucia Albertí Servera Llucia Albertí Servera 2Sina Nassiri Sina Nassiri 2Stephan Schmeing Stephan Schmeing 2Steffen Dettling Steffen Dettling 1Bhavesh Soni Bhavesh Soni 3Meher Majety Meher Majety 1Anne B. Krug Anne B. Krug 4Sabine Hoves Sabine Hoves 1Monika J. Wolf Monika J. Wolf 1*
  • 1 Roche Pharma Research and Early Development (pRED), Roche Innovation Center Munich, Penzberg, Germany
  • 2 Roche Pharma Research and Early Development (pRED), Roche Innovation Center Basel, Basel, Switzerland
  • 3 Roche Pharma Research and Early Development (pRED), Roche Innovation Center Zurich, Zürich, Switzerland
  • 4 Institute for Immunology, BioMedical Center, Ludwig Maximilian University of Munich, München, Bavaria, Germany

The final, formatted version of the article will be published soon.

    Plasmacytoid dendritic cells (pDCs) are capable of triggering broad immune responses, yet, their scarcity in blood coupled to their reduced functionality in cancer, makes their therapeutic use for in situ activation or vaccination challenging. We designed an in vitro differentiation protocol tailored for human pDCs from cord-blood (CB) hematopoietic stem cells and report the generation of 200 pDCs per hematopoietic stem cell. We highlight the role of StemRegenin 1 and GM-CSF supplementation in enhancing IFN-α responses. In-depth characterization of CB-pDCs revealed a robust resemblance to primary pDCs phenotypically and functionally. Transcriptomic analysis confirmed strong homology both at baseline and upon TLR9 or TLR7 stimulation. Further, we could confirm the potential of CB-pDCs to elicit cytokines associated with NK and T cell recruitment and cytolytic functions upon TLR7-stimulation ex vivo in patient tumor explants. This study highlights CB-pDCs as surrogates for primary pDCs and their potential for cell therapy in cancer.

    Keywords: Dendritic cell differentiation, Hematopoietic stem cells (HSCS), human, DC vaccination, cancer immunotherapy, Plasmacytoid dendritic cells (pDCs)

    Received: 15 May 2024; Accepted: 09 Oct 2024.

    Copyright: © 2024 Fiore, Weckwarth, Paetzold, Albertí Servera, Nassiri, Schmeing, Dettling, Soni, Majety, Krug, Hoves and Wolf. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Monika J. Wolf, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Munich, Penzberg, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.