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Front. Immunol. | doi: 10.3389/fimmu.2019.00602

Neoadjuvant radiochemotherapy significantly alters the phenotype of plasmacytoid dendritic cells and 6-sulfo LacNAc+ monocytes in rectal cancer

 Felix Wagner1, Ulrike Hölig1,  Friederike Wilczkowski1,  Ulrich Sommer2, Rebekka Wehner1,  Max Kiessler1,  Armin Jarosch2,  Ioana Plesca1, Katharina Flecke1, Maia Arsova1, Antje Tunger1, Andreas Bogner3,  Christoph Reißfelder4, Jürgen Weitz3,  Knut Schäkel5, Esther Troost6, Mechthild Krause6, Gunnar Folprecht7, Martin Bornhäuser7, Michael P. Bachmann8, Daniela Aust2, Gustavo Baretton2 and  Marc Schmitz9*
  • 1Institut für Immunologie, Medizinische Fakultät, Technische Universität Dresden, Germany
  • 2Institut für Pathologie, Universitätsklinikum Carl Gustav Carus, Germany
  • 3Abteilung für Viszeral, Thorax und Gefäßchirurgie, Universitätsklinikum Carl Gustav Carus, Germany
  • 4Klinik für Chirurgie,Universitätsmedizin Mannheim (UMM), Germany
  • 5Hautklinik Universitätsklinikum Heidelberg, Germany
  • 6Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Germany
  • 7Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Germany
  • 8Abteilung für Radioimmunologie, Institut für Radiopharmazeutische Krebsforschung, Helmholtz-Zentrum Dresden-Rossendorf, Germany
  • 9Institute of Immunology, Faculty of Medicine, Technical University of Dresden, Germany

Neoadjuvant radiochemotherapy (nRCT) can significantly influence the tumor immune architecture that plays a pivotal role in regulating tumor growth. Whereas various studies have investigated the effect of nRCT on tumor-infiltrating T cells, little is known about its impact on the frequency and activation status of human dendritic cells (DCs). Plasmacytoid DCs (pDCs) essentially contribute to the regulation of innate and adaptive immunity and may profoundly influence tumor progression. Recent studies have revealed that higher pDC numbers are associated with poor prognosis in cancer patients. 6-sulfo LacNAc-expressing monocytes (slanMo) represent a particular proinflammatory subset of human non-classical blood monocytes that can differentiate into DCs. Recently, we have reported that activated slanMo produce various proinflammatory cytokines and efficiently stimulate natural killer cells and T lymphocytes. slanMo were also shown to accumulate in clear cell renal cell carcinoma and in metastatic lymph nodes from cancer patients. Here, we investigated the influence of nRCT on the frequency of rectal cancer-infiltrating pDCs and slanMo. When evaluating rectal cancer tissues obtained from patients after nRCT, a significantly higher density of pDCs in comparison to pre-nRCT tissue samples was found. In contrast, the density of slanMo was not significantly altered by nRCT. Further studies revealed that nRCT significantly enhances the proportion of rectal cancer-infiltrating CD8+ T cells expressing the cytotoxic effector molecule granzyme B. When exploring the impact of nRCT on the phenotype of rectal cancer-infiltrating pDCs and slanMo, we observed that nRCT markedly enhances the percentage of inducible nitric oxide synthase- or tumor necrosis factor alpha-producing slanMo. Furthermore, nRCT significantly increased the percentage of mature CD83+ pDCs in rectal cancer tissues. Moreover, the proportion of pDCs locally expressing interferon-alpha, which plays a major role in antitumor immunity, was significantly higher in post-nRCT tissues compared to pre-nRCT tumor specimens. These novel findings indicate that nRCT significantly influences the frequency and/or phenotype of pDCs, slanMo, and CD8+ T cells, which may influence the clinical response of rectal cancer patients to nRCT.

Keywords: plasmacytoid dendritic cells, 6-sulfo LacNAc+ monocytes, tumor immune architecture, radiochemotherapy, rectal cancer

Received: 28 Aug 2018; Accepted: 06 Mar 2019.

Edited by:

Silvia B. Boscardin, University of São Paulo, Brazil

Reviewed by:

Veronika Lukacs-Kornek, Saarland University, Germany
Shohei Koyama, Osaka University, Japan  

Copyright: © 2019 Wagner, Hölig, Wilczkowski, Sommer, Wehner, Kiessler, Jarosch, Plesca, Flecke, Arsova, Tunger, Bogner, Reißfelder, Weitz, Schäkel, Troost, Krause, Folprecht, Bornhäuser, Bachmann, Aust, Baretton and Schmitz. 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) and the copyright owner(s) 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: Prof. Marc Schmitz, Faculty of Medicine, Technical University of Dresden, Institute of Immunology, Dresden, Germany,