The Bilateral Interplay between Cancer Immunotherapies and Neutrophils’ Phenotypes and Sub-Populations
Immunotherapy has become a leading modality for the treatment of cancer, but despite its increasing success, a substantial number of patients do not benefit from it. Cancer-related neutrophils have become, in recent years, a subject of growing interest. Distinct sub-populations of neutrophils have b...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/5/783 |
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| author | Naomi Kaisar-Iluz Ludovica Arpinati Merav E. Shaul Sojod Mahroum Mohamad Qaisi Einat Tidhar Zvi G. Fridlender |
| author_facet | Naomi Kaisar-Iluz Ludovica Arpinati Merav E. Shaul Sojod Mahroum Mohamad Qaisi Einat Tidhar Zvi G. Fridlender |
| author_sort | Naomi Kaisar-Iluz |
| collection | DOAJ |
| description | Immunotherapy has become a leading modality for the treatment of cancer, but despite its increasing success, a substantial number of patients do not benefit from it. Cancer-related neutrophils have become, in recent years, a subject of growing interest. Distinct sub-populations of neutrophils have been identified at advanced stages of cancer. In this study, we aimed to evaluate the role of neutrophils in mediating the efficacy of immune checkpoint inhibitors (ICI) treatments (α-PD-1/PD-L1), by assessing lung tumor models in mice. We found that G-CSF overexpression by the tumor significantly potentiates the efficacy of ICI, whereas neutrophils’ depletion abrogated their responses. Adoptive transfer of circulating normal-density neutrophils (NDN) resulted in significantly reduced tumor growth, whereas low-density neutrophils (LDN) had no effect. We next investigated the effect of ICI on neutrophils’ functions. Following α-PD-L1 treatment, NDN displayed increased ROS production and increased cytotoxicity toward tumor cells but decreased degranulation. Together, our results suggest that neutrophils are important mediators of the ICI treatments and that mainly NDN are modulated following α-PD-L1 treatment. This research provides a better understanding of the function of neutrophils following immunotherapies and their impact on the efficacy of immunotherapy, supporting better understanding and future improvement of currently available treatments. |
| first_indexed | 2024-03-09T20:44:36Z |
| format | Article |
| id | doaj.art-4e7b950436154917be39858cc5981ab7 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:44:36Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-4e7b950436154917be39858cc5981ab72023-11-23T22:50:11ZengMDPI AGCells2073-44092022-02-0111578310.3390/cells11050783The Bilateral Interplay between Cancer Immunotherapies and Neutrophils’ Phenotypes and Sub-PopulationsNaomi Kaisar-Iluz0Ludovica Arpinati1Merav E. Shaul2Sojod Mahroum3Mohamad Qaisi4Einat Tidhar5Zvi G. Fridlender6Institute of Pulmonary Medicine, Hadassah Medical Center, Jerusalem 91120, IsraelInstitute of Pulmonary Medicine, Hadassah Medical Center, Jerusalem 91120, IsraelInstitute of Pulmonary Medicine, Hadassah Medical Center, Jerusalem 91120, IsraelInstitute of Pulmonary Medicine, Hadassah Medical Center, Jerusalem 91120, IsraelInstitute of Pulmonary Medicine, Hadassah Medical Center, Jerusalem 91120, IsraelInstitute of Pulmonary Medicine, Hadassah Medical Center, Jerusalem 91120, IsraelInstitute of Pulmonary Medicine, Hadassah Medical Center, Jerusalem 91120, IsraelImmunotherapy has become a leading modality for the treatment of cancer, but despite its increasing success, a substantial number of patients do not benefit from it. Cancer-related neutrophils have become, in recent years, a subject of growing interest. Distinct sub-populations of neutrophils have been identified at advanced stages of cancer. In this study, we aimed to evaluate the role of neutrophils in mediating the efficacy of immune checkpoint inhibitors (ICI) treatments (α-PD-1/PD-L1), by assessing lung tumor models in mice. We found that G-CSF overexpression by the tumor significantly potentiates the efficacy of ICI, whereas neutrophils’ depletion abrogated their responses. Adoptive transfer of circulating normal-density neutrophils (NDN) resulted in significantly reduced tumor growth, whereas low-density neutrophils (LDN) had no effect. We next investigated the effect of ICI on neutrophils’ functions. Following α-PD-L1 treatment, NDN displayed increased ROS production and increased cytotoxicity toward tumor cells but decreased degranulation. Together, our results suggest that neutrophils are important mediators of the ICI treatments and that mainly NDN are modulated following α-PD-L1 treatment. This research provides a better understanding of the function of neutrophils following immunotherapies and their impact on the efficacy of immunotherapy, supporting better understanding and future improvement of currently available treatments.https://www.mdpi.com/2073-4409/11/5/783neutrophilslung cancerimmunotherapyPD-L1PD-1G-CSF |
| spellingShingle | Naomi Kaisar-Iluz Ludovica Arpinati Merav E. Shaul Sojod Mahroum Mohamad Qaisi Einat Tidhar Zvi G. Fridlender The Bilateral Interplay between Cancer Immunotherapies and Neutrophils’ Phenotypes and Sub-Populations Cells neutrophils lung cancer immunotherapy PD-L1 PD-1 G-CSF |
| title | The Bilateral Interplay between Cancer Immunotherapies and Neutrophils’ Phenotypes and Sub-Populations |
| title_full | The Bilateral Interplay between Cancer Immunotherapies and Neutrophils’ Phenotypes and Sub-Populations |
| title_fullStr | The Bilateral Interplay between Cancer Immunotherapies and Neutrophils’ Phenotypes and Sub-Populations |
| title_full_unstemmed | The Bilateral Interplay between Cancer Immunotherapies and Neutrophils’ Phenotypes and Sub-Populations |
| title_short | The Bilateral Interplay between Cancer Immunotherapies and Neutrophils’ Phenotypes and Sub-Populations |
| title_sort | bilateral interplay between cancer immunotherapies and neutrophils phenotypes and sub populations |
| topic | neutrophils lung cancer immunotherapy PD-L1 PD-1 G-CSF |
| url | https://www.mdpi.com/2073-4409/11/5/783 |
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