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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1473897
This article is part of the Research Topic Community Series in Novel Biomarkers in Tumor Immunity and Immunotherapy: Volume II View all 13 articles

Suppression of MCP-1, IFN-γ and IL-6 production of HNSCC ex vivo by pembrolizumab added to docetaxel and cisplatin (TP) exceeding those of TP alone is linked to improved survival

Provisionally accepted
Jana Wellhausen Jana Wellhausen 1Louisa Röhl Louisa Röhl 1Michael Berszin Michael Berszin 1Irene Krücken Irene Krücken 2,3Veit Zebralla Veit Zebralla 1,3Markus Pirlich Markus Pirlich 1,3Matthaeus Stoehr Matthaeus Stoehr 1,3Susanne Wiegand Susanne Wiegand 1,3,4Andreas Dietz Andreas Dietz 1,3Theresa Wald Theresa Wald 1,3Gunnar Wichmann Gunnar Wichmann 1,3*
  • 1 Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig, Leipzig, Lower Saxony, Germany
  • 2 Institute of Pathology, University Hospital Leipzig, Leipzig, Lower Saxony, Germany
  • 3 The Comprehensive Cancer Center Central Germany, Leipzig University Hospital, Leipzig, Germany
  • 4 Department of Otorhinolaryngology, Head and Neck Surgery, Faculty of Medicine, University of Kiel, Kiel, Schleswig-Holstein, Germany

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

    Background: Adding pembrolizumab, an anti-PD-1 antibody approved for treatment of head and neck squamous cell carcinoma (HNSCC) to neoadjuvant (induction-) chemotherapy utilizing docetaxel and cisplatin (TP) followed by radiotherapy may improve outcome in larynx organ-preservation (LOP) that is investigated in the European Larynx-Organ preservation Study (ELOS). As biomarkers for response to TP and pembrolizumab +TP are missing but may include cytokines, this work aims on determining cytokines potentially linked to outcome as prognostic markers sufficient to predict and/or monitor response to successful LOP.Collagenase IV digests were generated from 47 histopathological confirmed HNSCC tumor samples and seeded in 96-well plates containing pembrolizumab, docetaxel, cisplatin either solely or in binary or ternary combination. According to the FLAVINO protocol, supernatants were collected after 3 days, adherent cells fixed using ethanol, air-dried and pan-cytokeratin positive epithelial cells counted using fluorescence microscopy. The cytokines IL-6, IL-8, IFN-γ, IP-10, MCP-1, TNF-α, and VEGF in the supernatant were quantified by sandwich ELISA.The mode of interaction between pembrolizumab and TP was assessed and correlated to outcome (overall, disease-specific and progression-free survival of patients). Suppression of MCP-1, IFN-γ and IL-6 production by pembrolizumab + TP exceeding the suppressive effect of TP was detected in the majority of samples and linked to improved survival. Multivariate Cox proportional hazard regression modeling revealed MCP-1, IFN-γ and IL-6 as independent outcome predictors.Conclusions: Comparing response to TP vs. pembrolizumab vs. TP + pembrolizumab may allow for identification of patients with superior outcome independent from treatment applied.

    Keywords: PD-1:PD-L1 immune-checkpoint inhibitor (ICI) pembrolizumab, local and locoregional advanced head and neck squamous cell carcinoma (HNSCC), neoadjuvant (induction) chemotherapy, predictive assay for chemoresponse-evaluation, Biomarker research, monocyte chemoattractant protein 1 (MCP-1, CCL2)

    Received: 31 Jul 2024; Accepted: 19 Dec 2024.

    Copyright: © 2024 Wellhausen, Röhl, Berszin, Krücken, Zebralla, Pirlich, Stoehr, Wiegand, Dietz, Wald and Wichmann. 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: Gunnar Wichmann, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig, Leipzig, Lower Saxony, 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.