SPI1+CD68+ macrophages as a biomarker for gastric cancer metastasis: a rationale for combined antiangiogenic and immunotherapy strategies
Background Tumor-associated macrophages (TAMs) have been demonstrated to be associated with tumor progression. However, the different subpopulations of TAMs and their roles in gastric cancer (GC) remain poorly understood. This study aims to assess the effects of Spi-1 proto-oncogene (SPI1)+CD68+ TAM...
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| Language: | English |
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BMJ Publishing Group
2024-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/10/e009983.full |
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| author | Hong Yu Yulong He Changhua Zhang Zhenzhen Zhao Guofei Deng Pengliang Wang Rishun Su Xuezeng Sun Zizhen Wu Zhangsen Huang Liang Gu Mingyu Huo Songcheng Yin |
| author_facet | Hong Yu Yulong He Changhua Zhang Zhenzhen Zhao Guofei Deng Pengliang Wang Rishun Su Xuezeng Sun Zizhen Wu Zhangsen Huang Liang Gu Mingyu Huo Songcheng Yin |
| author_sort | Hong Yu |
| collection | DOAJ |
| description | Background Tumor-associated macrophages (TAMs) have been demonstrated to be associated with tumor progression. However, the different subpopulations of TAMs and their roles in gastric cancer (GC) remain poorly understood. This study aims to assess the effects of Spi-1 proto-oncogene (SPI1)+CD68+ TAMs in GC.Methods The distribution of SPI1+CD68+ TAMs in GC tissue was estimated by immunohistochemistry, immunofluorescence, and flow cytometry. Single-cell transcriptome analysis and multiplex fluorescence immunohistochemistry were applied to explore the role of SPI1+CD68+ TAMs in an immune contexture. SPI1 overexpression or knockdown cells were constructed to evaluate its role in macrophage polarization and angiogenesis in vitro and in vivo. Chromatin immunoprecipitation was used to verify the mechanism of SPI1 transcriptional function. The effect of combined antiangiogenic and immunotherapy was further validated using mouse peritoneal metastasis models.Results Single-cell transcriptome analysis and immunohistochemistry demonstrated that SPI1 was expressed in macrophages, with a higher enrichment in metastatic lesions than in primary tumors. Higher SPI1+CD68+ TAMs infiltration was associated with poor overall survival. Mechanically, SPI1 promoted the M2-type macrophage polarization. SPI1 could bind to the promoter of vascular endothelial growth factor A and facilitate angiogenesis. Moreover, the level of SPI1+CD68+ TAMs infiltration was closely related to the efficacy of immunotherapy, especially when combined with antiangiogenic therapy.Conclusions The present study showed that SPI1+CD68+ TAMs are a promising biomarker for predicting prognosis, antiangiogenic drug sensitivity, and combination target of immunotherapy in patients with GC. |
| format | Article |
| id | doaj-art-0c7699cae5984ee6bde48c3dde2d34f4 |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-0c7699cae5984ee6bde48c3dde2d34f42025-08-20T02:14:20ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-10-01121010.1136/jitc-2024-009983SPI1+CD68+ macrophages as a biomarker for gastric cancer metastasis: a rationale for combined antiangiogenic and immunotherapy strategiesHong Yu0Yulong He1Changhua Zhang2Zhenzhen Zhao3Guofei Deng4Pengliang Wang5Rishun Su6Xuezeng Sun7Zizhen Wu8Zhangsen Huang9Liang Gu10Mingyu Huo11Songcheng Yin12Digestive Diseases Center, The Seventh Affiliated Hospital Sun Yat-sen University, Shenzhen, Guangdong, ChinaDigestive Diseases Center, The Seventh Affiliated Hospital Sun Yat-sen University, Shenzhen, Guangdong, ChinaDigestive Diseases Center, The Seventh Affiliated Hospital Sun Yat-sen University, Shenzhen, Guangdong, ChinaDigestive Diseases Center, The Seventh Affiliated Hospital Sun Yat-sen University, Shenzhen, Guangdong, ChinaDigestive Diseases Center, The Seventh Affiliated Hospital Sun Yat-sen University, Shenzhen, Guangdong, ChinaDepartment of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, ChinaDigestive Diseases Center, The Seventh Affiliated Hospital Sun Yat-sen University, Shenzhen, Guangdong, ChinaDigestive Diseases Center, The Seventh Affiliated Hospital Sun Yat-sen University, Shenzhen, Guangdong, ChinaDepartment of Gastroenterological Surgery, Peking University People’s Hospital, Beijing, ChinaDigestive Diseases Center, The Seventh Affiliated Hospital Sun Yat-sen University, Shenzhen, Guangdong, ChinaDigestive Diseases Center, The Seventh Affiliated Hospital Sun Yat-sen University, Shenzhen, Guangdong, ChinaDigestive Diseases Center, The Seventh Affiliated Hospital Sun Yat-sen University, Shenzhen, Guangdong, ChinaDigestive Diseases Center, The Seventh Affiliated Hospital Sun Yat-sen University, Shenzhen, Guangdong, ChinaBackground Tumor-associated macrophages (TAMs) have been demonstrated to be associated with tumor progression. However, the different subpopulations of TAMs and their roles in gastric cancer (GC) remain poorly understood. This study aims to assess the effects of Spi-1 proto-oncogene (SPI1)+CD68+ TAMs in GC.Methods The distribution of SPI1+CD68+ TAMs in GC tissue was estimated by immunohistochemistry, immunofluorescence, and flow cytometry. Single-cell transcriptome analysis and multiplex fluorescence immunohistochemistry were applied to explore the role of SPI1+CD68+ TAMs in an immune contexture. SPI1 overexpression or knockdown cells were constructed to evaluate its role in macrophage polarization and angiogenesis in vitro and in vivo. Chromatin immunoprecipitation was used to verify the mechanism of SPI1 transcriptional function. The effect of combined antiangiogenic and immunotherapy was further validated using mouse peritoneal metastasis models.Results Single-cell transcriptome analysis and immunohistochemistry demonstrated that SPI1 was expressed in macrophages, with a higher enrichment in metastatic lesions than in primary tumors. Higher SPI1+CD68+ TAMs infiltration was associated with poor overall survival. Mechanically, SPI1 promoted the M2-type macrophage polarization. SPI1 could bind to the promoter of vascular endothelial growth factor A and facilitate angiogenesis. Moreover, the level of SPI1+CD68+ TAMs infiltration was closely related to the efficacy of immunotherapy, especially when combined with antiangiogenic therapy.Conclusions The present study showed that SPI1+CD68+ TAMs are a promising biomarker for predicting prognosis, antiangiogenic drug sensitivity, and combination target of immunotherapy in patients with GC.https://jitc.bmj.com/content/12/10/e009983.full |
| spellingShingle | Hong Yu Yulong He Changhua Zhang Zhenzhen Zhao Guofei Deng Pengliang Wang Rishun Su Xuezeng Sun Zizhen Wu Zhangsen Huang Liang Gu Mingyu Huo Songcheng Yin SPI1+CD68+ macrophages as a biomarker for gastric cancer metastasis: a rationale for combined antiangiogenic and immunotherapy strategies Journal for ImmunoTherapy of Cancer |
| title | SPI1+CD68+ macrophages as a biomarker for gastric cancer metastasis: a rationale for combined antiangiogenic and immunotherapy strategies |
| title_full | SPI1+CD68+ macrophages as a biomarker for gastric cancer metastasis: a rationale for combined antiangiogenic and immunotherapy strategies |
| title_fullStr | SPI1+CD68+ macrophages as a biomarker for gastric cancer metastasis: a rationale for combined antiangiogenic and immunotherapy strategies |
| title_full_unstemmed | SPI1+CD68+ macrophages as a biomarker for gastric cancer metastasis: a rationale for combined antiangiogenic and immunotherapy strategies |
| title_short | SPI1+CD68+ macrophages as a biomarker for gastric cancer metastasis: a rationale for combined antiangiogenic and immunotherapy strategies |
| title_sort | spi1 cd68 macrophages as a biomarker for gastric cancer metastasis a rationale for combined antiangiogenic and immunotherapy strategies |
| url | https://jitc.bmj.com/content/12/10/e009983.full |
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