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
BackgroundAdding 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 invest...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1473897/full |
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| author | Jana Wellhausen Louisa Röhl Michael Berszin Irene Krücken Irene Krücken Veit Zebralla Veit Zebralla Markus Pirlich Markus Pirlich Matthaeus Stoehr Matthaeus Stoehr Susanne Wiegand Susanne Wiegand Susanne Wiegand Andreas Dietz Andreas Dietz Theresa Wald Theresa Wald Gunnar Wichmann Gunnar Wichmann |
| author_facet | Jana Wellhausen Louisa Röhl Michael Berszin Irene Krücken Irene Krücken Veit Zebralla Veit Zebralla Markus Pirlich Markus Pirlich Matthaeus Stoehr Matthaeus Stoehr Susanne Wiegand Susanne Wiegand Susanne Wiegand Andreas Dietz Andreas Dietz Theresa Wald Theresa Wald Gunnar Wichmann Gunnar Wichmann |
| author_sort | Jana Wellhausen |
| collection | DOAJ |
| description | BackgroundAdding 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.MethodsCollagenase 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.ResultsThe 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.ConclusionsComparing response to TP vs. pembrolizumab vs. TP + pembrolizumab may allow for identification of patients with superior outcome independent from treatment applied. |
| format | Article |
| id | doaj-art-def9c76c6fa549e2af7333622468b965 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-def9c76c6fa549e2af7333622468b9652025-01-15T05:10:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14738971473897Suppression 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 survivalJana Wellhausen0Louisa Röhl1Michael Berszin2Irene Krücken3Irene Krücken4Veit Zebralla5Veit Zebralla6Markus Pirlich7Markus Pirlich8Matthaeus Stoehr9Matthaeus Stoehr10Susanne Wiegand11Susanne Wiegand12Susanne Wiegand13Andreas Dietz14Andreas Dietz15Theresa Wald16Theresa Wald17Gunnar Wichmann18Gunnar Wichmann19Department of Otorhinolaryngology, Head and Neck surgery, University Hospital Leipzig, Leipzig, GermanyDepartment of Otorhinolaryngology, Head and Neck surgery, University Hospital Leipzig, Leipzig, GermanyDepartment of Otorhinolaryngology, Head and Neck surgery, University Hospital Leipzig, Leipzig, GermanyInstitute of Pathology, University Hospital Leipzig, Leipzig, GermanyThe Comprehensive Cancer Center Central Germany, Leipzig University Hospital, Leipzig, GermanyDepartment of Otorhinolaryngology, Head and Neck surgery, University Hospital Leipzig, Leipzig, GermanyThe Comprehensive Cancer Center Central Germany, Leipzig University Hospital, Leipzig, GermanyDepartment of Otorhinolaryngology, Head and Neck surgery, University Hospital Leipzig, Leipzig, GermanyThe Comprehensive Cancer Center Central Germany, Leipzig University Hospital, Leipzig, GermanyDepartment of Otorhinolaryngology, Head and Neck surgery, University Hospital Leipzig, Leipzig, GermanyThe Comprehensive Cancer Center Central Germany, Leipzig University Hospital, Leipzig, GermanyDepartment of Otorhinolaryngology, Head and Neck surgery, University Hospital Leipzig, Leipzig, GermanyThe Comprehensive Cancer Center Central Germany, Leipzig University Hospital, Leipzig, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, Christian-Albrechts-University Kiel, Kiel, GermanyDepartment of Otorhinolaryngology, Head and Neck surgery, University Hospital Leipzig, Leipzig, GermanyThe Comprehensive Cancer Center Central Germany, Leipzig University Hospital, Leipzig, GermanyDepartment of Otorhinolaryngology, Head and Neck surgery, University Hospital Leipzig, Leipzig, GermanyThe Comprehensive Cancer Center Central Germany, Leipzig University Hospital, Leipzig, GermanyDepartment of Otorhinolaryngology, Head and Neck surgery, University Hospital Leipzig, Leipzig, GermanyThe Comprehensive Cancer Center Central Germany, Leipzig University Hospital, Leipzig, GermanyBackgroundAdding 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.MethodsCollagenase 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.ResultsThe 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.ConclusionsComparing response to TP vs. pembrolizumab vs. TP + pembrolizumab may allow for identification of patients with superior outcome independent from treatment applied.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1473897/fullPD-1:PD-L1 immune-checkpoint inhibitor (ICI) pembrolizumablocal and locoregional advanced head and neck squamous cell carcinoma (HNSCC)neoadjuvant (induction) chemotherapypredictive assay for chemoresponse-evaluationbiomarker researchmonocyte chemoattractant protein 1 (MCP-1 |
| spellingShingle | Jana Wellhausen Louisa Röhl Michael Berszin Irene Krücken Irene Krücken Veit Zebralla Veit Zebralla Markus Pirlich Markus Pirlich Matthaeus Stoehr Matthaeus Stoehr Susanne Wiegand Susanne Wiegand Susanne Wiegand Andreas Dietz Andreas Dietz Theresa Wald Theresa Wald Gunnar Wichmann Gunnar Wichmann 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 Frontiers in Immunology 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | 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 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1473897/full |
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