CD215+ Myeloid Cells Respond to Interleukin 15 Stimulation and Promote Tumor Progression
Interleukin 15 (IL-15) regulates the development, survival, and functions of multiple innate and adaptive immune cells and plays a dual role in promoting both tumor cell growth and antitumor immunity. Here, we demonstrated that the in vivo injection of recombinant human IL-15 (200 µg/kg) or murine I...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01713/full |
| _version_ | 1828255245520601088 |
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| author | Shouheng Lin Shouheng Lin Shouheng Lin Guohua Huang Yiren Xiao Yiren Xiao Yiren Xiao Wei Sun Wei Sun Wei Sun Yuchuan Jiang Qiuhua Deng Muyun Peng Xinru Wei Xinru Wei Wei Ye Wei Ye Baiheng Li Baiheng Li Simiao Lin Simiao Lin Suna Wang Suna Wang Qiting Wu Qiting Wu Qiubin Liang Yangqiu Li Xuchao Zhang Yilong Wu Pentao Liu Duanqing Pei Duanqing Pei Fenglei Yu Zhesheng Wen Yao Yao Yao Yao Donghai Wu Donghai Wu Peng Li Peng Li Peng Li |
| author_facet | Shouheng Lin Shouheng Lin Shouheng Lin Guohua Huang Yiren Xiao Yiren Xiao Yiren Xiao Wei Sun Wei Sun Wei Sun Yuchuan Jiang Qiuhua Deng Muyun Peng Xinru Wei Xinru Wei Wei Ye Wei Ye Baiheng Li Baiheng Li Simiao Lin Simiao Lin Suna Wang Suna Wang Qiting Wu Qiting Wu Qiubin Liang Yangqiu Li Xuchao Zhang Yilong Wu Pentao Liu Duanqing Pei Duanqing Pei Fenglei Yu Zhesheng Wen Yao Yao Yao Yao Donghai Wu Donghai Wu Peng Li Peng Li Peng Li |
| author_sort | Shouheng Lin |
| collection | DOAJ |
| description | Interleukin 15 (IL-15) regulates the development, survival, and functions of multiple innate and adaptive immune cells and plays a dual role in promoting both tumor cell growth and antitumor immunity. Here, we demonstrated that the in vivo injection of recombinant human IL-15 (200 µg/kg) or murine IL-15 (3 µg/kg) to tumor-bearing NOD-SCID-IL2Rg−/− (NSI) mice resulted in increased tumor progression and CD45+ CD11b+ Gr-1+ CD215+ cell expansion in the tumors and spleen. In B16F10-bearing C57BL/6 mice model, we found that murine IL-15 has antitumoral effect since the activation and expansion of CD8+ T cells with murine IL-15 treatment. But no enhanced or reduced tumor growth was observed in mice when human IL-15 was used. However, both murine and human IL-15 promote CD45+ CD11b+ Gr-1+ CD215+ cells expansion. In xenograft tumor models, CD215+ myeloid cells, but not CD215− cells, responded to human IL-15 stimulation and promoted tumor growth. Furthermore, we found that human IL-15 mediated insulin-like growth factor-1 production in CD215+ myeloid cells and blocking IGF-1 reduced the tumor-promoting effect of IL-15. Finally, we observed that higher IGF-1 expression is an indicator of poor prognosis among lung adenocarcinoma patients. These findings provide evidence that IL-15 may promote tumor cell progression via CD215+ myeloid cells, and IGF-1 may be an important candidate that IL-15 facilitates tumor growth. |
| first_indexed | 2024-04-13T02:11:41Z |
| format | Article |
| id | doaj.art-96f2c4549cc744b3808ed4bdd0b8a695 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T02:11:41Z |
| publishDate | 2017-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-96f2c4549cc744b3808ed4bdd0b8a6952022-12-22T03:07:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-12-01810.3389/fimmu.2017.01713296978CD215+ Myeloid Cells Respond to Interleukin 15 Stimulation and Promote Tumor ProgressionShouheng Lin0Shouheng Lin1Shouheng Lin2Guohua Huang3Yiren Xiao4Yiren Xiao5Yiren Xiao6Wei Sun7Wei Sun8Wei Sun9Yuchuan Jiang10Qiuhua Deng11Muyun Peng12Xinru Wei13Xinru Wei14Wei Ye15Wei Ye16Baiheng Li17Baiheng Li18Simiao Lin19Simiao Lin20Suna Wang21Suna Wang22Qiting Wu23Qiting Wu24Qiubin Liang25Yangqiu Li26Xuchao Zhang27Yilong Wu28Pentao Liu29Duanqing Pei30Duanqing Pei31Fenglei Yu32Zhesheng Wen33Yao Yao34Yao Yao35Donghai Wu36Donghai Wu37Peng Li38Peng Li39Peng Li40Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaDepartment of Respiratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaKey Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaKey Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaDepartment of Thoracic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Respiratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Thoracic Oncology, The Second Xiangya Hospital of Central South University, Changsha, ChinaKey Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong Zhaotai InVivo Biomedicine Co. Ltd., Guangzhou, ChinaMedical College, Institute of Hematology, Jinan University, Guangzhou, ChinaGuangdong Lung Cancer Institute, Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaGuangdong Lung Cancer Institute, Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China0Wellcome Trust Sanger Institute, Hinxton, United KingdomKey Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaDepartment of Thoracic Oncology, The Second Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Thoracic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaKey Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaKey Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China1International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, ChinaInterleukin 15 (IL-15) regulates the development, survival, and functions of multiple innate and adaptive immune cells and plays a dual role in promoting both tumor cell growth and antitumor immunity. Here, we demonstrated that the in vivo injection of recombinant human IL-15 (200 µg/kg) or murine IL-15 (3 µg/kg) to tumor-bearing NOD-SCID-IL2Rg−/− (NSI) mice resulted in increased tumor progression and CD45+ CD11b+ Gr-1+ CD215+ cell expansion in the tumors and spleen. In B16F10-bearing C57BL/6 mice model, we found that murine IL-15 has antitumoral effect since the activation and expansion of CD8+ T cells with murine IL-15 treatment. But no enhanced or reduced tumor growth was observed in mice when human IL-15 was used. However, both murine and human IL-15 promote CD45+ CD11b+ Gr-1+ CD215+ cells expansion. In xenograft tumor models, CD215+ myeloid cells, but not CD215− cells, responded to human IL-15 stimulation and promoted tumor growth. Furthermore, we found that human IL-15 mediated insulin-like growth factor-1 production in CD215+ myeloid cells and blocking IGF-1 reduced the tumor-promoting effect of IL-15. Finally, we observed that higher IGF-1 expression is an indicator of poor prognosis among lung adenocarcinoma patients. These findings provide evidence that IL-15 may promote tumor cell progression via CD215+ myeloid cells, and IGF-1 may be an important candidate that IL-15 facilitates tumor growth.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01713/fullinterleukin 15CD215IGF-1patient-derived xenograftlung cancer |
| spellingShingle | Shouheng Lin Shouheng Lin Shouheng Lin Guohua Huang Yiren Xiao Yiren Xiao Yiren Xiao Wei Sun Wei Sun Wei Sun Yuchuan Jiang Qiuhua Deng Muyun Peng Xinru Wei Xinru Wei Wei Ye Wei Ye Baiheng Li Baiheng Li Simiao Lin Simiao Lin Suna Wang Suna Wang Qiting Wu Qiting Wu Qiubin Liang Yangqiu Li Xuchao Zhang Yilong Wu Pentao Liu Duanqing Pei Duanqing Pei Fenglei Yu Zhesheng Wen Yao Yao Yao Yao Donghai Wu Donghai Wu Peng Li Peng Li Peng Li CD215+ Myeloid Cells Respond to Interleukin 15 Stimulation and Promote Tumor Progression Frontiers in Immunology interleukin 15 CD215 IGF-1 patient-derived xenograft lung cancer |
| title | CD215+ Myeloid Cells Respond to Interleukin 15 Stimulation and Promote Tumor Progression |
| title_full | CD215+ Myeloid Cells Respond to Interleukin 15 Stimulation and Promote Tumor Progression |
| title_fullStr | CD215+ Myeloid Cells Respond to Interleukin 15 Stimulation and Promote Tumor Progression |
| title_full_unstemmed | CD215+ Myeloid Cells Respond to Interleukin 15 Stimulation and Promote Tumor Progression |
| title_short | CD215+ Myeloid Cells Respond to Interleukin 15 Stimulation and Promote Tumor Progression |
| title_sort | cd215 myeloid cells respond to interleukin 15 stimulation and promote tumor progression |
| topic | interleukin 15 CD215 IGF-1 patient-derived xenograft lung cancer |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01713/full |
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