The IL-25/ILC2 axis promotes lung cancer with a concomitant accumulation of immune-suppressive cells in tumors in humans and mice
BackgroundGroup 2 innate lymphoid cells (ILC2) can be activated by interleukin (IL)-33 or IL-25. IL-25-activated ILC2 cells help protect the host against helminth infection while exacerbating allergic-like inflammation and tissue damage in the lung. In the context of cancer, IL-33-activated ILC2 cel...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1244437/full |
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| author | Ilham Bahhar Ilham Bahhar Zeynep Eş Zeynep Eş Oğuzhan Köse Oğuzhan Köse Akif Turna Mehmet Zeki Günlüoğlu Aslı Çakır Deniz Duralı Deniz Duralı Deniz Duralı Fay C. Magnusson Fay C. Magnusson Fay C. Magnusson |
| author_facet | Ilham Bahhar Ilham Bahhar Zeynep Eş Zeynep Eş Oğuzhan Köse Oğuzhan Köse Akif Turna Mehmet Zeki Günlüoğlu Aslı Çakır Deniz Duralı Deniz Duralı Deniz Duralı Fay C. Magnusson Fay C. Magnusson Fay C. Magnusson |
| author_sort | Ilham Bahhar |
| collection | DOAJ |
| description | BackgroundGroup 2 innate lymphoid cells (ILC2) can be activated by interleukin (IL)-33 or IL-25. IL-25-activated ILC2 cells help protect the host against helminth infection while exacerbating allergic-like inflammation and tissue damage in the lung. In the context of cancer, IL-33-activated ILC2 cells were found to bear anti-tumoral functions in lung cancer while IL-25-activated ILC2 cells promoted tumorigenesis in colorectal cancer. The role of IL-25-activated ILC2 cells in lung cancer remains to be addressed.MethodsWe examined the overall survival of human non-small cell lung cancer (NSCLC) patients according to IL25 expression as well as the distribution of ILC2 cells and regulatory T cells (Tregs) in various NSCLC patient tissues and peripheral blood (PB) of healthy donors (HDs). We analyzed the effect of adoptive transfer of IL-25-activated ILC2 cells on tumor growth, metastasis and survival in a heterotopic murine model of lung cancer.ResultsWe report that human NSCLC patients with high IL-25 expression have reduced overall survival. Moreover, NSCLC patients bear increased frequencies of ILC2s compared to HDs. Frequencies of Tregs were also increased in NSCLC patients, concomitantly with ILC2s. In mice bearing heterotopic lung cancer, adoptive transfer of IL-25-activated ILC2s led to increased tumor growth, increased metastasis and reduced survival. The frequencies of monocytic myeloid-derived suppressor cells (M-MDSCs) were found to be increased in the tumors of mice that received ILC2s as compared to controls.ConclusionOverall, our results indicate that the IL-25/ILC2 axis promotes lung cancer potentially by recruiting immune-suppressive cells to the tumors both in humans and in mice, and that it may therefore represent a suitable novel target for NSCLC immunotherapeutic development. |
| first_indexed | 2024-03-12T00:01:21Z |
| format | Article |
| id | doaj.art-aff68cfe3e584322b2a13ac9c58fb208 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T00:01:21Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-aff68cfe3e584322b2a13ac9c58fb2082023-09-18T03:11:33ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12444371244437The IL-25/ILC2 axis promotes lung cancer with a concomitant accumulation of immune-suppressive cells in tumors in humans and miceIlham Bahhar0Ilham Bahhar1Zeynep Eş2Zeynep Eş3Oğuzhan Köse4Oğuzhan Köse5Akif Turna6Mehmet Zeki Günlüoğlu7Aslı Çakır8Deniz Duralı9Deniz Duralı10Deniz Duralı11Fay C. Magnusson12Fay C. Magnusson13Fay C. Magnusson14Cancer Research Center, Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, TürkiyeRegenerative and Restorative Medicine Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, TürkiyeCancer Research Center, Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, TürkiyeRegenerative and Restorative Medicine Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, TürkiyeCancer Research Center, Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, TürkiyeRegenerative and Restorative Medicine Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, TürkiyeDepartment of Thoracic Surgery, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, Fatih, Istanbul, TürkiyeDepartment of Thoracic Surgery, Faculty of Medicine, Istanbul Medipol University, Istanbul, TürkiyeDepartment of Pathology, Faculty of Medicine, Istanbul Medipol University, Istanbul, TürkiyeCancer Research Center, Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, TürkiyeRegenerative and Restorative Medicine Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, TürkiyeDepartment of Medical Microbiology, International School of Medicine, Istanbul Medipol University, Istanbul, TürkiyeCancer Research Center, Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, TürkiyeRegenerative and Restorative Medicine Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, Istanbul, TürkiyeDepartment of Medical Microbiology, International School of Medicine, Istanbul Medipol University, Istanbul, TürkiyeBackgroundGroup 2 innate lymphoid cells (ILC2) can be activated by interleukin (IL)-33 or IL-25. IL-25-activated ILC2 cells help protect the host against helminth infection while exacerbating allergic-like inflammation and tissue damage in the lung. In the context of cancer, IL-33-activated ILC2 cells were found to bear anti-tumoral functions in lung cancer while IL-25-activated ILC2 cells promoted tumorigenesis in colorectal cancer. The role of IL-25-activated ILC2 cells in lung cancer remains to be addressed.MethodsWe examined the overall survival of human non-small cell lung cancer (NSCLC) patients according to IL25 expression as well as the distribution of ILC2 cells and regulatory T cells (Tregs) in various NSCLC patient tissues and peripheral blood (PB) of healthy donors (HDs). We analyzed the effect of adoptive transfer of IL-25-activated ILC2 cells on tumor growth, metastasis and survival in a heterotopic murine model of lung cancer.ResultsWe report that human NSCLC patients with high IL-25 expression have reduced overall survival. Moreover, NSCLC patients bear increased frequencies of ILC2s compared to HDs. Frequencies of Tregs were also increased in NSCLC patients, concomitantly with ILC2s. In mice bearing heterotopic lung cancer, adoptive transfer of IL-25-activated ILC2s led to increased tumor growth, increased metastasis and reduced survival. The frequencies of monocytic myeloid-derived suppressor cells (M-MDSCs) were found to be increased in the tumors of mice that received ILC2s as compared to controls.ConclusionOverall, our results indicate that the IL-25/ILC2 axis promotes lung cancer potentially by recruiting immune-suppressive cells to the tumors both in humans and in mice, and that it may therefore represent a suitable novel target for NSCLC immunotherapeutic development.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1244437/fullinnate lymphoid cells group 2non-small cell lung cancermyeloid-derived suppressor cellsregulatory T lymphocytesinnate immunityadoptive transfer |
| spellingShingle | Ilham Bahhar Ilham Bahhar Zeynep Eş Zeynep Eş Oğuzhan Köse Oğuzhan Köse Akif Turna Mehmet Zeki Günlüoğlu Aslı Çakır Deniz Duralı Deniz Duralı Deniz Duralı Fay C. Magnusson Fay C. Magnusson Fay C. Magnusson The IL-25/ILC2 axis promotes lung cancer with a concomitant accumulation of immune-suppressive cells in tumors in humans and mice Frontiers in Immunology innate lymphoid cells group 2 non-small cell lung cancer myeloid-derived suppressor cells regulatory T lymphocytes innate immunity adoptive transfer |
| title | The IL-25/ILC2 axis promotes lung cancer with a concomitant accumulation of immune-suppressive cells in tumors in humans and mice |
| title_full | The IL-25/ILC2 axis promotes lung cancer with a concomitant accumulation of immune-suppressive cells in tumors in humans and mice |
| title_fullStr | The IL-25/ILC2 axis promotes lung cancer with a concomitant accumulation of immune-suppressive cells in tumors in humans and mice |
| title_full_unstemmed | The IL-25/ILC2 axis promotes lung cancer with a concomitant accumulation of immune-suppressive cells in tumors in humans and mice |
| title_short | The IL-25/ILC2 axis promotes lung cancer with a concomitant accumulation of immune-suppressive cells in tumors in humans and mice |
| title_sort | il 25 ilc2 axis promotes lung cancer with a concomitant accumulation of immune suppressive cells in tumors in humans and mice |
| topic | innate lymphoid cells group 2 non-small cell lung cancer myeloid-derived suppressor cells regulatory T lymphocytes innate immunity adoptive transfer |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1244437/full |
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