Checkpoint Inhibitors Modulate Plasticity of Innate Lymphoid Cells in Peripheral Blood of Patients With Hepatocellular Carcinoma
Innate lymphoid cells (ILC) are a heterogeneous and plastic population of cells of the innate immune system. Their role in cancer and specifically in hepatocellular carcinoma is unraveling. The presence of ILCs in peripheral blood of HCC patients has not been explored yet. Their role and function in...
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| Format: | Article |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.849958/full |
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| author | Bernd Heinrich Bernd Heinrich Benjamin Ruf Varun Subramanyam Yuta Myojin Chunwei W. Lai Chunwei W. Lai Amanda J. Craig Jianyang Fu Changqing Xie Alexander Kroemer Tim F. Greten Tim F. Greten Firouzeh Korangy |
| author_facet | Bernd Heinrich Bernd Heinrich Benjamin Ruf Varun Subramanyam Yuta Myojin Chunwei W. Lai Chunwei W. Lai Amanda J. Craig Jianyang Fu Changqing Xie Alexander Kroemer Tim F. Greten Tim F. Greten Firouzeh Korangy |
| author_sort | Bernd Heinrich |
| collection | DOAJ |
| description | Innate lymphoid cells (ILC) are a heterogeneous and plastic population of cells of the innate immune system. Their role in cancer and specifically in hepatocellular carcinoma is unraveling. The presence of ILCs in peripheral blood of HCC patients has not been explored yet. Their role and function in response to checkpoint inhibitor therapy have also not been explored. Here, we characterized ILCs in PBMC of HCC patients at baseline and after treatment with immune checkpoint inhibitors (ICI) by flow cytometry and single-cell sequencing. Characterization of ILC subsets in PBMCs of HCC patients showed a significant increase in ILC1 and a decrease in ILC3 frequencies. Single-cell RNA-sequencing identified a subgroup of NK-like ILCs which expressed cytotoxicity markers as well as NKp80/KLRF1. This KLRF1high NK-like population showed low abundance in patients with HCC and was enhanced after combined anti-CTLA-4 and anti-PD-1immunotherapy. Trajectory analysis placed this population in between ILC1 and ILC3 cells. The transcriptomic signature of KLRF1high NK-like ILCs was associated with better progression-free survival in large HCC cohorts. This study shows a previously unknown effect of ICI on the composition and plasticity of ILCS in peripheral blood. Thus, ILCs from PBMC can be used to study changes in the innate immune system under immunotherapy. |
| first_indexed | 2024-04-13T17:01:53Z |
| format | Article |
| id | doaj.art-e3c2fc3658ac4359a1a365321add0534 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T17:01:53Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e3c2fc3658ac4359a1a365321add05342022-12-22T02:38:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.849958849958Checkpoint Inhibitors Modulate Plasticity of Innate Lymphoid Cells in Peripheral Blood of Patients With Hepatocellular CarcinomaBernd Heinrich0Bernd Heinrich1Benjamin Ruf2Varun Subramanyam3Yuta Myojin4Chunwei W. Lai5Chunwei W. Lai6Amanda J. Craig7Jianyang Fu8Changqing Xie9Alexander Kroemer10Tim F. Greten11Tim F. Greten12Firouzeh Korangy13Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesDepartment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, GermanyThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD, United StatesLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United StatesThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesMedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital and the Center for Translational Transplant Medicine, Georgetown University Medical Center, Washington, DC, United StatesThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesNational Cancer Institute, Center for Cancer Research (NCI CCR) Liver Cancer Program, National Institutes of Health, Bethesda, MD, United StatesThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesInnate lymphoid cells (ILC) are a heterogeneous and plastic population of cells of the innate immune system. Their role in cancer and specifically in hepatocellular carcinoma is unraveling. The presence of ILCs in peripheral blood of HCC patients has not been explored yet. Their role and function in response to checkpoint inhibitor therapy have also not been explored. Here, we characterized ILCs in PBMC of HCC patients at baseline and after treatment with immune checkpoint inhibitors (ICI) by flow cytometry and single-cell sequencing. Characterization of ILC subsets in PBMCs of HCC patients showed a significant increase in ILC1 and a decrease in ILC3 frequencies. Single-cell RNA-sequencing identified a subgroup of NK-like ILCs which expressed cytotoxicity markers as well as NKp80/KLRF1. This KLRF1high NK-like population showed low abundance in patients with HCC and was enhanced after combined anti-CTLA-4 and anti-PD-1immunotherapy. Trajectory analysis placed this population in between ILC1 and ILC3 cells. The transcriptomic signature of KLRF1high NK-like ILCs was associated with better progression-free survival in large HCC cohorts. This study shows a previously unknown effect of ICI on the composition and plasticity of ILCS in peripheral blood. Thus, ILCs from PBMC can be used to study changes in the innate immune system under immunotherapy.https://www.frontiersin.org/articles/10.3389/fimmu.2022.849958/fullcheckpoint inhibitorsanti-PD-1anti-CTLA-4innate lymphoid cellsNK-cellshepatocellular carcinoma |
| spellingShingle | Bernd Heinrich Bernd Heinrich Benjamin Ruf Varun Subramanyam Yuta Myojin Chunwei W. Lai Chunwei W. Lai Amanda J. Craig Jianyang Fu Changqing Xie Alexander Kroemer Tim F. Greten Tim F. Greten Firouzeh Korangy Checkpoint Inhibitors Modulate Plasticity of Innate Lymphoid Cells in Peripheral Blood of Patients With Hepatocellular Carcinoma Frontiers in Immunology checkpoint inhibitors anti-PD-1 anti-CTLA-4 innate lymphoid cells NK-cells hepatocellular carcinoma |
| title | Checkpoint Inhibitors Modulate Plasticity of Innate Lymphoid Cells in Peripheral Blood of Patients With Hepatocellular Carcinoma |
| title_full | Checkpoint Inhibitors Modulate Plasticity of Innate Lymphoid Cells in Peripheral Blood of Patients With Hepatocellular Carcinoma |
| title_fullStr | Checkpoint Inhibitors Modulate Plasticity of Innate Lymphoid Cells in Peripheral Blood of Patients With Hepatocellular Carcinoma |
| title_full_unstemmed | Checkpoint Inhibitors Modulate Plasticity of Innate Lymphoid Cells in Peripheral Blood of Patients With Hepatocellular Carcinoma |
| title_short | Checkpoint Inhibitors Modulate Plasticity of Innate Lymphoid Cells in Peripheral Blood of Patients With Hepatocellular Carcinoma |
| title_sort | checkpoint inhibitors modulate plasticity of innate lymphoid cells in peripheral blood of patients with hepatocellular carcinoma |
| topic | checkpoint inhibitors anti-PD-1 anti-CTLA-4 innate lymphoid cells NK-cells hepatocellular carcinoma |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.849958/full |
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