Surgical Stress Abrogates Pre-Existing Protective T Cell Mediated Anti-Tumor Immunity Leading to Postoperative Cancer Recurrence.
Anti-tumor CD8+ T cells are a key determinant for overall survival in patients following surgical resection for solid malignancies. Using a mouse model of cancer vaccination (adenovirus expressing melanoma tumor-associated antigen (TAA)-dopachrome tautomerase (AdDCT) and resection resulting in major...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4873120?pdf=render |
| _version_ | 1811228833421983744 |
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| author | Abhirami A Ananth Lee-Hwa Tai Casey Lansdell Almohanad A Alkayyal Katherine E Baxter Leonard Angka Jiqing Zhang Christiano Tanese de Souza Kyle B Stephenson Kelley Parato Jonathan L Bramson John C Bell Brian D Lichty Rebecca C Auer |
| author_facet | Abhirami A Ananth Lee-Hwa Tai Casey Lansdell Almohanad A Alkayyal Katherine E Baxter Leonard Angka Jiqing Zhang Christiano Tanese de Souza Kyle B Stephenson Kelley Parato Jonathan L Bramson John C Bell Brian D Lichty Rebecca C Auer |
| author_sort | Abhirami A Ananth |
| collection | DOAJ |
| description | Anti-tumor CD8+ T cells are a key determinant for overall survival in patients following surgical resection for solid malignancies. Using a mouse model of cancer vaccination (adenovirus expressing melanoma tumor-associated antigen (TAA)-dopachrome tautomerase (AdDCT) and resection resulting in major surgical stress (abdominal nephrectomy), we demonstrate that surgical stress results in a reduction in the number of CD8+ T cell that produce cytokines (IFNγ, TNFα, Granzyme B) in response to TAA. This effect is secondary to both reduced proliferation and impaired T cell function following antigen binding. In a prophylactic model, surgical stress completely abrogates tumor protection conferred by vaccination in the immediate postoperative period. In a clinically relevant surgical resection model, vaccinated mice undergoing a positive margin resection with surgical stress had decreased survival compared to mice with positive margin resection alone. Preoperative immunotherapy with IFNα significantly extends survival in surgically stressed mice. Importantly, myeloid derived suppressor cell (MDSC) population numbers and functional impairment of TAA-specific CD8+ T cell were altered in surgically stressed mice. Our observations suggest that cancer progression may result from surgery-induced suppression of tumor-specific CD8+ T cells. Preoperative immunotherapies aimed at targeting the prometastatic effects of cancer surgery will reduce recurrence and improve survival in cancer surgery patients. |
| first_indexed | 2024-04-12T10:02:59Z |
| format | Article |
| id | doaj.art-551c7ca1f5e9471199f644eceec99f59 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T10:02:59Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-551c7ca1f5e9471199f644eceec99f592022-12-22T03:37:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01115e015594710.1371/journal.pone.0155947Surgical Stress Abrogates Pre-Existing Protective T Cell Mediated Anti-Tumor Immunity Leading to Postoperative Cancer Recurrence.Abhirami A AnanthLee-Hwa TaiCasey LansdellAlmohanad A AlkayyalKatherine E BaxterLeonard AngkaJiqing ZhangChristiano Tanese de SouzaKyle B StephensonKelley ParatoJonathan L BramsonJohn C BellBrian D LichtyRebecca C AuerAnti-tumor CD8+ T cells are a key determinant for overall survival in patients following surgical resection for solid malignancies. Using a mouse model of cancer vaccination (adenovirus expressing melanoma tumor-associated antigen (TAA)-dopachrome tautomerase (AdDCT) and resection resulting in major surgical stress (abdominal nephrectomy), we demonstrate that surgical stress results in a reduction in the number of CD8+ T cell that produce cytokines (IFNγ, TNFα, Granzyme B) in response to TAA. This effect is secondary to both reduced proliferation and impaired T cell function following antigen binding. In a prophylactic model, surgical stress completely abrogates tumor protection conferred by vaccination in the immediate postoperative period. In a clinically relevant surgical resection model, vaccinated mice undergoing a positive margin resection with surgical stress had decreased survival compared to mice with positive margin resection alone. Preoperative immunotherapy with IFNα significantly extends survival in surgically stressed mice. Importantly, myeloid derived suppressor cell (MDSC) population numbers and functional impairment of TAA-specific CD8+ T cell were altered in surgically stressed mice. Our observations suggest that cancer progression may result from surgery-induced suppression of tumor-specific CD8+ T cells. Preoperative immunotherapies aimed at targeting the prometastatic effects of cancer surgery will reduce recurrence and improve survival in cancer surgery patients.http://europepmc.org/articles/PMC4873120?pdf=render |
| spellingShingle | Abhirami A Ananth Lee-Hwa Tai Casey Lansdell Almohanad A Alkayyal Katherine E Baxter Leonard Angka Jiqing Zhang Christiano Tanese de Souza Kyle B Stephenson Kelley Parato Jonathan L Bramson John C Bell Brian D Lichty Rebecca C Auer Surgical Stress Abrogates Pre-Existing Protective T Cell Mediated Anti-Tumor Immunity Leading to Postoperative Cancer Recurrence. PLoS ONE |
| title | Surgical Stress Abrogates Pre-Existing Protective T Cell Mediated Anti-Tumor Immunity Leading to Postoperative Cancer Recurrence. |
| title_full | Surgical Stress Abrogates Pre-Existing Protective T Cell Mediated Anti-Tumor Immunity Leading to Postoperative Cancer Recurrence. |
| title_fullStr | Surgical Stress Abrogates Pre-Existing Protective T Cell Mediated Anti-Tumor Immunity Leading to Postoperative Cancer Recurrence. |
| title_full_unstemmed | Surgical Stress Abrogates Pre-Existing Protective T Cell Mediated Anti-Tumor Immunity Leading to Postoperative Cancer Recurrence. |
| title_short | Surgical Stress Abrogates Pre-Existing Protective T Cell Mediated Anti-Tumor Immunity Leading to Postoperative Cancer Recurrence. |
| title_sort | surgical stress abrogates pre existing protective t cell mediated anti tumor immunity leading to postoperative cancer recurrence |
| url | http://europepmc.org/articles/PMC4873120?pdf=render |
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