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Image_1_PD-1 blockade attenuates surgery-mediated immunosuppression and boosts Th1 immunity perioperatively in oesophagogastric junctional adenocarcinoma.pdf
| العنوان: | Image_1_PD-1 blockade attenuates surgery-mediated immunosuppression and boosts Th1 immunity perioperatively in oesophagogastric junctional adenocarcinoma.pdf |
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| المؤلفون: | Maria Davern, Caoimhe Gaughan, Fiona O’ Connell, Brendan Moran, Eimear Mylod, Andrew D. Sheppard, Sinead Ramjit, Jasmine Yun-Tong Kung, James J. Phelan, Matthew G. Davey, Eanna J. Ryan, Christine Butler, Laura Quinn, Claudine Howard, Emily Tone, Eimear Phoenix, Waqas T. Butt, Niamh Lynam-Lennon, Stephen G. Maher, Narayanasamy Ravi, Claire L. Donohoe, John V. Reynolds, Joanne Lysaght, Noel E. Donlon |
| سنة النشر: | 2023 |
| المجموعة: | Frontiers: Figshare |
| مصطلحات موضوعية: | Immunology, Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies), Autoimmunity, Cellular Immunology, Humoural Immunology and Immunochemistry, Immunogenetics (incl. Genetic Immunology), Innate Immunity, Transplantation Immunology, Tumour Immunology, Immunology not elsewhere classified, Genetic Immunology, Animal Immunology, Veterinary Immunology, nivolumab and ipilimumab, PD-1, TIGIT, perioperative, Th1 immunity, immunosuppression, surgery, oesophageal adenocarcinoma |
| الوصف: | Introduction This timely study assesses the immunosuppressive effects of surgery on cytotoxic Th1-like immunity and investigates if immune checkpoint blockade (ICB) can boost Th1-like immunity in the perioperative window in upper gastrointestinal cancer (UGI) patients. Methods PBMCs were isolated from 11 UGI patients undergoing tumour resection on post-operative days (POD) 0, 1, 7 and 42 and expanded ex vivo using anti-CD3/28 and IL-2 for 5 days in the absence/presence of nivolumab or ipilimumab. T cells were subsequently immunophenotyped via flow cytometry to determine the frequency of T helper (Th)1-like, Th1/17-like, Th17-like and regulatory T cell (Tregs) subsets and their immune checkpoint expression profile. Lymphocyte secretions were also assessed via multiplex ELISA (IFN-γ, granzyme B, IL-17 and IL-10). The 48h cytotoxic ability of vehicle-, nivolumab- and ipilimumab-expanded PBMCs isolated on POD 0, 1, 7 and 42 against radiosensitive and radioresistant oesophageal adenocarcinoma tumour cells (OE33 P and OE33 R) was also examined using a cell counting kit-8 (CCK-8) assay to determine if surgery affected the killing ability of lymphocytes and whether the use of ICB could enhance cytotoxicity. Results Th1-like immunity was suppressed in expanded PBMCs in the immediate post-operative setting. The frequency of expanded circulating Th1-like cells was significantly decreased post-operatively accompanied by a decrease in IFN-γ production and a concomitant increase in the frequency of expanded regulatory T cells with an increase in circulating levels of IL-10. Interestingly, PD-L1 and CTLA-4 immune checkpoint proteins were also upregulated on expanded Th1-like cells post-operatively. Additionally, the cytotoxic ability of expanded lymphocytes against oesophageal adenocarcinoma tumour cells was abrogated post-surgery. Of note, the addition of nivolumab or ipilimumab attenuated the surgery-mediated suppression of lymphocyte cytotoxicity, demonstrated by a significant increase in tumour cell killing and an increase ... |
| نوع الوثيقة: | still image |
| اللغة: | unknown |
| Relation: | https://figshare.com/articles/figure/Image_1_PD-1_blockade_attenuates_surgery-mediated_immunosuppression_and_boosts_Th1_immunity_perioperatively_in_oesophagogastric_junctional_adenocarcinoma_pdf/23439005 |
| DOI: | 10.3389/fimmu.2023.1150754.s001 |
| الاتاحة: | https://doi.org/10.3389/fimmu.2023.1150754.s001 https://figshare.com/articles/figure/Image_1_PD-1_blockade_attenuates_surgery-mediated_immunosuppression_and_boosts_Th1_immunity_perioperatively_in_oesophagogastric_junctional_adenocarcinoma_pdf/23439005 |
| Rights: | CC BY 4.0 |
| رقم الانضمام: | edsbas.988E8329 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fimmu.2023.1150754.s001 |
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