Immune checkpoint blockade induced shifts in cytokine expression patterns in peripheral blood of head and neck cancer patients are linked to outcome
BackgroundImmune-checkpoint blockade (ICB) of programmed-death-1 (PD-1) with pembrolizumab or nivolumab is approved for treating recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). NadiHN and ADRISK are phase IIB trials investigating in locally advanced (LA) HNSCC having low or...
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1237623/full |
| _version_ | 1797668193541554176 |
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| author | Louisa Röhl Jana Wellhausen Michael Berszin Irene Krücken Veit Zebralla Markus Pirlich Susanne Wiegand Andreas Dietz Theresa Wald Gunnar Wichmann |
| author_facet | Louisa Röhl Jana Wellhausen Michael Berszin Irene Krücken Veit Zebralla Markus Pirlich Susanne Wiegand Andreas Dietz Theresa Wald Gunnar Wichmann |
| author_sort | Louisa Röhl |
| collection | DOAJ |
| description | BackgroundImmune-checkpoint blockade (ICB) of programmed-death-1 (PD-1) with pembrolizumab or nivolumab is approved for treating recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). NadiHN and ADRISK are phase IIB trials investigating in locally advanced (LA) HNSCC having low or high risk of recurrence the potential benefits from adding nivolumab to post-operative radiotherapy or pembrolizumab to cisplatin-based radio-chemotherapy.MethodsAlong five randomized controlled ICB trials including NadiHN and ADRISK, blood samples were taken before and after starting ICB in n=25 patients. Concentrations of vascular endothelial growth factor A (VEGF), CCL2 (MCP-1), interleukin-6 (IL-6), IL-8, interferon-gamma (IFN-γ), and CXCL10 (IP-10) pre- and post-ICB in EDTA-anticoagulated plasma and serum were compared. We used receiver operating characteristic (ROC) curves to identify optimal cutoff for defining subgroups before analyzing overall survival (OS) applying Kaplan–Meier plots and multivariate Cox regression.ResultsWe detected huge heterogeneity between cytokine patterns in pre-and post-ICB plasma and serum. We observed high correlation between concentrations of some cytokines. Despite absent systematic OS differences after ICB with pembrolizumab or nivolumab or between LA-HNSCC versus R/M HNSCC patients, we noticed improved outcome of patients having lower IFN-γ concentrations pre- and post-ICB and following ICB reduced concentrations of VEGF, IL-6, and IL-8 but not MCP-1. Contrarily, increases in IL-6, IL-8, and VEGF levels correlated with impaired outcome. Multivariate Cox regression revealed five independent OS predictors among cytokines; using natural logarithms of their hazard ratios to estimate an individual’s risk of dying, three cytokine-expression pattern (CEP)-risk groups with no death within mean (95% confidence interval) follow-up of 29.2 (22.1–36.2) months and median OS of 11.3 (8.8–13.8) and 2.9 (0.4-5.4) months were found.ConclusionWhereas individual pre- or post-ICB cytokine concentrations in serum or plasma alone failed to predict the survivor group, CEP-risk groups may support the identification of individual patients with long-lasting benefit from ICB. |
| first_indexed | 2024-03-11T20:25:02Z |
| format | Article |
| id | doaj.art-2844b68fdef74e30ab5deaea9b3f11fe |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T20:25:02Z |
| publishDate | 2023-10-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-2844b68fdef74e30ab5deaea9b3f11fe2023-10-02T15:11:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12376231237623Immune checkpoint blockade induced shifts in cytokine expression patterns in peripheral blood of head and neck cancer patients are linked to outcomeLouisa Röhl0Jana Wellhausen1Michael Berszin2Irene Krücken3Veit Zebralla4Markus Pirlich5Susanne Wiegand6Andreas Dietz7Theresa Wald8Gunnar Wichmann9Department 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, GermanyDepartment 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, GermanyDepartment 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, GermanyBackgroundImmune-checkpoint blockade (ICB) of programmed-death-1 (PD-1) with pembrolizumab or nivolumab is approved for treating recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). NadiHN and ADRISK are phase IIB trials investigating in locally advanced (LA) HNSCC having low or high risk of recurrence the potential benefits from adding nivolumab to post-operative radiotherapy or pembrolizumab to cisplatin-based radio-chemotherapy.MethodsAlong five randomized controlled ICB trials including NadiHN and ADRISK, blood samples were taken before and after starting ICB in n=25 patients. Concentrations of vascular endothelial growth factor A (VEGF), CCL2 (MCP-1), interleukin-6 (IL-6), IL-8, interferon-gamma (IFN-γ), and CXCL10 (IP-10) pre- and post-ICB in EDTA-anticoagulated plasma and serum were compared. We used receiver operating characteristic (ROC) curves to identify optimal cutoff for defining subgroups before analyzing overall survival (OS) applying Kaplan–Meier plots and multivariate Cox regression.ResultsWe detected huge heterogeneity between cytokine patterns in pre-and post-ICB plasma and serum. We observed high correlation between concentrations of some cytokines. Despite absent systematic OS differences after ICB with pembrolizumab or nivolumab or between LA-HNSCC versus R/M HNSCC patients, we noticed improved outcome of patients having lower IFN-γ concentrations pre- and post-ICB and following ICB reduced concentrations of VEGF, IL-6, and IL-8 but not MCP-1. Contrarily, increases in IL-6, IL-8, and VEGF levels correlated with impaired outcome. Multivariate Cox regression revealed five independent OS predictors among cytokines; using natural logarithms of their hazard ratios to estimate an individual’s risk of dying, three cytokine-expression pattern (CEP)-risk groups with no death within mean (95% confidence interval) follow-up of 29.2 (22.1–36.2) months and median OS of 11.3 (8.8–13.8) and 2.9 (0.4-5.4) months were found.ConclusionWhereas individual pre- or post-ICB cytokine concentrations in serum or plasma alone failed to predict the survivor group, CEP-risk groups may support the identification of individual patients with long-lasting benefit from ICB.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1237623/fullimmune checkpoint inhibitor-blockade (ICB)programmed-death 1 (PD-1)head and neck squamous cell carcinoma (HNSCC)liquid biopsycytokine expression pattern (CEP)interferon gamma (IFN-γ) |
| spellingShingle | Louisa Röhl Jana Wellhausen Michael Berszin Irene Krücken Veit Zebralla Markus Pirlich Susanne Wiegand Andreas Dietz Theresa Wald Gunnar Wichmann Immune checkpoint blockade induced shifts in cytokine expression patterns in peripheral blood of head and neck cancer patients are linked to outcome Frontiers in Immunology immune checkpoint inhibitor-blockade (ICB) programmed-death 1 (PD-1) head and neck squamous cell carcinoma (HNSCC) liquid biopsy cytokine expression pattern (CEP) interferon gamma (IFN-γ) |
| title | Immune checkpoint blockade induced shifts in cytokine expression patterns in peripheral blood of head and neck cancer patients are linked to outcome |
| title_full | Immune checkpoint blockade induced shifts in cytokine expression patterns in peripheral blood of head and neck cancer patients are linked to outcome |
| title_fullStr | Immune checkpoint blockade induced shifts in cytokine expression patterns in peripheral blood of head and neck cancer patients are linked to outcome |
| title_full_unstemmed | Immune checkpoint blockade induced shifts in cytokine expression patterns in peripheral blood of head and neck cancer patients are linked to outcome |
| title_short | Immune checkpoint blockade induced shifts in cytokine expression patterns in peripheral blood of head and neck cancer patients are linked to outcome |
| title_sort | immune checkpoint blockade induced shifts in cytokine expression patterns in peripheral blood of head and neck cancer patients are linked to outcome |
| topic | immune checkpoint inhibitor-blockade (ICB) programmed-death 1 (PD-1) head and neck squamous cell carcinoma (HNSCC) liquid biopsy cytokine expression pattern (CEP) interferon gamma (IFN-γ) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1237623/full |
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