SAA suppresses α-PD-1 induced anti-tumor immunity by driving TH2 polarization in lung adenocarcinoma
Abstract Cancer stem cells (CSCs) are believed to be crucial in the initiation, progression, and recurrence of cancer. CSCs are also known to be more resistant to cancer treatments. However, the interaction between CSCs and the immune microenvironment is complex and not fully understood. In current...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-11-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-06198-w |
| _version_ | 1797636598609739776 |
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| author | Xin Wang Shaodi Wen Xiaoyue Du Yihan Zhang Xiao Yang Renrui Zou Bing Feng Xiao Fu Feng Jiang Guoren Zhou Zi Liu Wei Zhu Rong Ma Jifeng Feng Bo Shen |
| author_facet | Xin Wang Shaodi Wen Xiaoyue Du Yihan Zhang Xiao Yang Renrui Zou Bing Feng Xiao Fu Feng Jiang Guoren Zhou Zi Liu Wei Zhu Rong Ma Jifeng Feng Bo Shen |
| author_sort | Xin Wang |
| collection | DOAJ |
| description | Abstract Cancer stem cells (CSCs) are believed to be crucial in the initiation, progression, and recurrence of cancer. CSCs are also known to be more resistant to cancer treatments. However, the interaction between CSCs and the immune microenvironment is complex and not fully understood. In current study we used single cell RNA sequence (scRNA-Seq, public dataset) technology to identify the characteristic of CSCs. We found that the lung adenocarcinoma cancer stem population is highly inflammatory and remodels the tumor microenvironment by secreting inflammatory factors, specifically the acute phase protein serum amyloid A (SAA). Next, we developed an ex-vivo autologous patient-derived organoids (PDOs) and peripheral blood mononuclear cells (PBMCs) co-culture model to evaluate the immune biological impact of SAA. We found that SAA not only promotes chemoresistance by inducing cancer stem transformation, but also restricts anti-tumor immunity and promotes tumor fibrosis by driving type 2 immunity, and α-SAA neutralization antibody could restrict treatment resistant and tumor fibrosis. Mechanically, we found that the malignant phenotype induced by SAA is dependent on P2X7 receptor. Our data indicate that cancer stem cells secreted SAA have significant biological impact to promote treatment resistant and tumor fibrosis by driving cancer stemness transformation and type 2 immunity polarization via P2X7 receptor. Notably, α-SAA neutralization antibody shows therapeutic potential by restricting these malignant phenotypes. |
| first_indexed | 2024-03-11T12:37:26Z |
| format | Article |
| id | doaj.art-30df20bc130c4976a12ed53e2c1791aa |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-11T12:37:26Z |
| publishDate | 2023-11-01 |
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| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-30df20bc130c4976a12ed53e2c1791aa2023-11-05T12:30:54ZengNature Publishing GroupCell Death and Disease2041-48892023-11-01141111210.1038/s41419-023-06198-wSAA suppresses α-PD-1 induced anti-tumor immunity by driving TH2 polarization in lung adenocarcinomaXin Wang0Shaodi Wen1Xiaoyue Du2Yihan Zhang3Xiao Yang4Renrui Zou5Bing Feng6Xiao Fu7Feng Jiang8Guoren Zhou9Zi Liu10Wei Zhu11Rong Ma12Jifeng Feng13Bo Shen14Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer ResearchDepartment of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer ResearchDepartment of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer ResearchDepartment of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer ResearchDepartment of Clinical Laboratory, Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer ResearchDepartment of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer ResearchDepartment of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer ResearchDepartment of General Surgery, Nanjing Drum Tower HospitalDepartment of Thoracic Surgery, Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer ResearchDepartment of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer ResearchNanjing Advanced Analysis Tech. (NAAT) Co., LTDSchool of Medicine, Jiangsu UniversityResearch Center for Clinical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical UniversityDepartment of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer ResearchDepartment of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer ResearchAbstract Cancer stem cells (CSCs) are believed to be crucial in the initiation, progression, and recurrence of cancer. CSCs are also known to be more resistant to cancer treatments. However, the interaction between CSCs and the immune microenvironment is complex and not fully understood. In current study we used single cell RNA sequence (scRNA-Seq, public dataset) technology to identify the characteristic of CSCs. We found that the lung adenocarcinoma cancer stem population is highly inflammatory and remodels the tumor microenvironment by secreting inflammatory factors, specifically the acute phase protein serum amyloid A (SAA). Next, we developed an ex-vivo autologous patient-derived organoids (PDOs) and peripheral blood mononuclear cells (PBMCs) co-culture model to evaluate the immune biological impact of SAA. We found that SAA not only promotes chemoresistance by inducing cancer stem transformation, but also restricts anti-tumor immunity and promotes tumor fibrosis by driving type 2 immunity, and α-SAA neutralization antibody could restrict treatment resistant and tumor fibrosis. Mechanically, we found that the malignant phenotype induced by SAA is dependent on P2X7 receptor. Our data indicate that cancer stem cells secreted SAA have significant biological impact to promote treatment resistant and tumor fibrosis by driving cancer stemness transformation and type 2 immunity polarization via P2X7 receptor. Notably, α-SAA neutralization antibody shows therapeutic potential by restricting these malignant phenotypes.https://doi.org/10.1038/s41419-023-06198-w |
| spellingShingle | Xin Wang Shaodi Wen Xiaoyue Du Yihan Zhang Xiao Yang Renrui Zou Bing Feng Xiao Fu Feng Jiang Guoren Zhou Zi Liu Wei Zhu Rong Ma Jifeng Feng Bo Shen SAA suppresses α-PD-1 induced anti-tumor immunity by driving TH2 polarization in lung adenocarcinoma Cell Death and Disease |
| title | SAA suppresses α-PD-1 induced anti-tumor immunity by driving TH2 polarization in lung adenocarcinoma |
| title_full | SAA suppresses α-PD-1 induced anti-tumor immunity by driving TH2 polarization in lung adenocarcinoma |
| title_fullStr | SAA suppresses α-PD-1 induced anti-tumor immunity by driving TH2 polarization in lung adenocarcinoma |
| title_full_unstemmed | SAA suppresses α-PD-1 induced anti-tumor immunity by driving TH2 polarization in lung adenocarcinoma |
| title_short | SAA suppresses α-PD-1 induced anti-tumor immunity by driving TH2 polarization in lung adenocarcinoma |
| title_sort | saa suppresses α pd 1 induced anti tumor immunity by driving th2 polarization in lung adenocarcinoma |
| url | https://doi.org/10.1038/s41419-023-06198-w |
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