Does surgery affect systemic immune response? a perioperative analysis of TGF-β, IL-8 and CD45RO
BackgroundThe options of (neo-)adjuvant immunotherapy in addition to surgery in the treatment of oral squamous cell carcinoma (OSCC) are steadily increasing, but patients do not always respond to therapy as intended. The objectives of this study were to investigate the systemic perioperative course...
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1307956/full |
| _version_ | 1797401420746457088 |
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| author | Leah Trumet Leah Trumet Leah Trumet Jutta Ries Jutta Ries Niclas Ivenz Niclas Ivenz Philip Sobl Philip Sobl Falk Wehrhan Falk Wehrhan Rainer Lutz Rainer Lutz Marco Kesting Marco Kesting Manuel Weber Manuel Weber |
| author_facet | Leah Trumet Leah Trumet Leah Trumet Jutta Ries Jutta Ries Niclas Ivenz Niclas Ivenz Philip Sobl Philip Sobl Falk Wehrhan Falk Wehrhan Rainer Lutz Rainer Lutz Marco Kesting Marco Kesting Manuel Weber Manuel Weber |
| author_sort | Leah Trumet |
| collection | DOAJ |
| description | BackgroundThe options of (neo-)adjuvant immunotherapy in addition to surgery in the treatment of oral squamous cell carcinoma (OSCC) are steadily increasing, but patients do not always respond to therapy as intended. The objectives of this study were to investigate the systemic perioperative course of the biomarkers CD45RO, TGF-β, and IL-8 in non-tumor-related minor and tumor-related major maxillofacial surgery and to perform association analyses with demographic and histomorphologic parameters. A deeper understanding of surgery-related changes in various of different immune biomarkers could help to better understand the immunologic consequences of surgery which could influence immunotherapeutic protocols.MethodsPeripheral whole blood from 38 patients was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR) at five different timepoints before and after maxillofacial surgery to detect changes in mRNA expression of the biomarkers TGF-β, IL-8 and CD45RO. All patients underwent general anesthesia to undergo either resection and free flap reconstruction for OSCC or minor maxillofacial surgery (controls). Statistical analysis was done using Mann-Whitney-U test, Wilcoxon test, and Spearman’s correlation.ResultsCompared to the preoperative expression, there was a significant postoperative downregulation of CD45RO, TGF-β and IL-8 until the 4th postoperative day (p ≤ 0.003) in OSCC patients. For TGF-β and IL-8, the reduction in expression was significant (p ≤ 0.004) compared to controls. By postoperative day 10, all analyzed parameters converged to baseline levels. Only CD45RO still showed a significant downregulation (p=0.024). Spearman analysis revealed a significant correlation between increased duration of surgery and perioperative reduction in peripheral blood expression of CD45RO, TGF-β and IL-8 (p ≤ 0.004). Perioperative changes in TGF-β and PD-L1 expression were shown to be not correlated. Preoperative TGF-β expression was significantly lower in patients with lymph node metastases (p=0.014).ConclusionWith regard to the analyzed parameters, major oncologic head-and-neck surgery does not seem to have long-lasting systemic immunologic effects. Reduced CD45RO might be an expression of transient systemic immunosuppression in response to major surgery. The association of duration of surgery with expression changes of immunologic markers supports efforts to keep the duration of surgery as short as possible. As perioperative TGF-β and PD-L1 expression changes are not associated, these results support further investigation of a combined perioperative anti-PD-1 and anti-TGF-β immunotherapy. |
| first_indexed | 2024-03-09T02:09:50Z |
| format | Article |
| id | doaj.art-72e746cdef664defaf5514106d357b33 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-09T02:09:50Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-72e746cdef664defaf5514106d357b332023-12-07T14:02:41ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-12-011310.3389/fonc.2023.13079561307956Does surgery affect systemic immune response? a perioperative analysis of TGF-β, IL-8 and CD45ROLeah Trumet0Leah Trumet1Leah Trumet2Jutta Ries3Jutta Ries4Niclas Ivenz5Niclas Ivenz6Philip Sobl7Philip Sobl8Falk Wehrhan9Falk Wehrhan10Rainer Lutz11Rainer Lutz12Marco Kesting13Marco Kesting14Manuel Weber15Manuel Weber16Department of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI) and Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyDepartment of Operative Dentistry and Periodontology, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyDepartment of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI) and Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyDepartment of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI) and Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyDepartment of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI) and Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyDepartment of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyPrivate Office for Maxillofacial Surgery, Freiberg, GermanyDepartment of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI) and Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyDepartment of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI) and Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyDepartment of Oral and Cranio-Maxillofacial Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyDeutsches Zentrum Immuntherapie (DZI) and Comprehensive Cancer Center Erlangen-EMN (CCC ER-EMN), Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, GermanyBackgroundThe options of (neo-)adjuvant immunotherapy in addition to surgery in the treatment of oral squamous cell carcinoma (OSCC) are steadily increasing, but patients do not always respond to therapy as intended. The objectives of this study were to investigate the systemic perioperative course of the biomarkers CD45RO, TGF-β, and IL-8 in non-tumor-related minor and tumor-related major maxillofacial surgery and to perform association analyses with demographic and histomorphologic parameters. A deeper understanding of surgery-related changes in various of different immune biomarkers could help to better understand the immunologic consequences of surgery which could influence immunotherapeutic protocols.MethodsPeripheral whole blood from 38 patients was analyzed by real-time quantitative polymerase chain reaction (RT-qPCR) at five different timepoints before and after maxillofacial surgery to detect changes in mRNA expression of the biomarkers TGF-β, IL-8 and CD45RO. All patients underwent general anesthesia to undergo either resection and free flap reconstruction for OSCC or minor maxillofacial surgery (controls). Statistical analysis was done using Mann-Whitney-U test, Wilcoxon test, and Spearman’s correlation.ResultsCompared to the preoperative expression, there was a significant postoperative downregulation of CD45RO, TGF-β and IL-8 until the 4th postoperative day (p ≤ 0.003) in OSCC patients. For TGF-β and IL-8, the reduction in expression was significant (p ≤ 0.004) compared to controls. By postoperative day 10, all analyzed parameters converged to baseline levels. Only CD45RO still showed a significant downregulation (p=0.024). Spearman analysis revealed a significant correlation between increased duration of surgery and perioperative reduction in peripheral blood expression of CD45RO, TGF-β and IL-8 (p ≤ 0.004). Perioperative changes in TGF-β and PD-L1 expression were shown to be not correlated. Preoperative TGF-β expression was significantly lower in patients with lymph node metastases (p=0.014).ConclusionWith regard to the analyzed parameters, major oncologic head-and-neck surgery does not seem to have long-lasting systemic immunologic effects. Reduced CD45RO might be an expression of transient systemic immunosuppression in response to major surgery. The association of duration of surgery with expression changes of immunologic markers supports efforts to keep the duration of surgery as short as possible. As perioperative TGF-β and PD-L1 expression changes are not associated, these results support further investigation of a combined perioperative anti-PD-1 and anti-TGF-β immunotherapy.https://www.frontiersin.org/articles/10.3389/fonc.2023.1307956/fullperioperative systemic changes of signaling pathways immune toleranceOSCCHNSCCsurgeryinterleukinsoral surgery |
| spellingShingle | Leah Trumet Leah Trumet Leah Trumet Jutta Ries Jutta Ries Niclas Ivenz Niclas Ivenz Philip Sobl Philip Sobl Falk Wehrhan Falk Wehrhan Rainer Lutz Rainer Lutz Marco Kesting Marco Kesting Manuel Weber Manuel Weber Does surgery affect systemic immune response? a perioperative analysis of TGF-β, IL-8 and CD45RO Frontiers in Oncology perioperative systemic changes of signaling pathways immune tolerance OSCC HNSCC surgery interleukins oral surgery |
| title | Does surgery affect systemic immune response? a perioperative analysis of TGF-β, IL-8 and CD45RO |
| title_full | Does surgery affect systemic immune response? a perioperative analysis of TGF-β, IL-8 and CD45RO |
| title_fullStr | Does surgery affect systemic immune response? a perioperative analysis of TGF-β, IL-8 and CD45RO |
| title_full_unstemmed | Does surgery affect systemic immune response? a perioperative analysis of TGF-β, IL-8 and CD45RO |
| title_short | Does surgery affect systemic immune response? a perioperative analysis of TGF-β, IL-8 and CD45RO |
| title_sort | does surgery affect systemic immune response a perioperative analysis of tgf β il 8 and cd45ro |
| topic | perioperative systemic changes of signaling pathways immune tolerance OSCC HNSCC surgery interleukins oral surgery |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1307956/full |
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