PD-L1-expressing natural killer cells predict favorable prognosis and response to PD-1/PD-L1 blockade in neuroblastoma
T/NK cell-based immunotherapy has achieved remarkable success in adult cancers but has limited efficacy in pediatric malignancies including high-risk neuroblastoma (NB). Immune defects of NB tumor microenvironment are poorly understood compared with adults. Here, we described the unique characterist...
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Taylor & Francis Group
2024-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2289738 |
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| author | Mengjia Song Yue Huang Ye Hong Juan Liu Jia Zhu Suying Lu Juan Wang Feifei Sun Junting Huang Jiaqian Xu Yan Tang Jian-Chuan Xia Yizhuo Zhang |
| author_facet | Mengjia Song Yue Huang Ye Hong Juan Liu Jia Zhu Suying Lu Juan Wang Feifei Sun Junting Huang Jiaqian Xu Yan Tang Jian-Chuan Xia Yizhuo Zhang |
| author_sort | Mengjia Song |
| collection | DOAJ |
| description | T/NK cell-based immunotherapy has achieved remarkable success in adult cancers but has limited efficacy in pediatric malignancies including high-risk neuroblastoma (NB). Immune defects of NB tumor microenvironment are poorly understood compared with adults. Here, we described the unique characteristics of NB immune contexture and determined the phenotype signatures of PD-L1-expressing CD8+ T and NK cells in NB tumors by systemically analyzing the spatial distribution of T and NK cells and the distinct expression of programmed death 1 (PD-1) and its ligand (PD-L1) in patients with NB. We found that PD-L1-expressing CD8+ T and NK cells in NB tumors were highly activated and functionally competent and associated with better clinical outcomes. Intratumoral NK cells were a favorable prognostic biomarker independent of CD8+ T cells, PD-1/PD-L1 expression, tumor stage, MYCN amplification, and risk classification. NK cells combined with anti-PD-1/PD-L1 antibodies showed potent antitumor activity against both MYCN-amplified and non-amplified NBs in vitro and in vivo, and PD-L1-expressing NK cells associated with improved antitumor efficacy. Collectively, we raise novel insights into the role of PD-L1 expression on CD8+ T-cell and NK-cell activation. We highlight the great potential of intratumoral NK cells in better defining risk stratification, and predicting survival and response to anti-PD-1/PD-L1 therapy in NB. These findings explain why single anti-PD-1/PD-L1 therapy may not be successful in NB, suggesting its combination with NK cell-adoptive cellular therapy as a promising strategy for relapsing/refractory NB. This study provides a potential prospect that patients with PD-L1-expressing NK cells may respond to anti-PD-1/PD-L1 therapy. |
| format | Article |
| id | doaj-art-41a714b5f152460d9ce7ed1b9c1247f9 |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-41a714b5f152460d9ce7ed1b9c1247f92024-12-03T13:49:34ZengTaylor & Francis GroupOncoImmunology2162-402X2024-12-0113110.1080/2162402X.2023.2289738PD-L1-expressing natural killer cells predict favorable prognosis and response to PD-1/PD-L1 blockade in neuroblastomaMengjia Song0Yue Huang1Ye Hong2Juan Liu3Jia Zhu4Suying Lu5Juan Wang6Feifei Sun7Junting Huang8Jiaqian Xu9Yan Tang10Jian-Chuan Xia11Yizhuo Zhang12Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, ChinaT/NK cell-based immunotherapy has achieved remarkable success in adult cancers but has limited efficacy in pediatric malignancies including high-risk neuroblastoma (NB). Immune defects of NB tumor microenvironment are poorly understood compared with adults. Here, we described the unique characteristics of NB immune contexture and determined the phenotype signatures of PD-L1-expressing CD8+ T and NK cells in NB tumors by systemically analyzing the spatial distribution of T and NK cells and the distinct expression of programmed death 1 (PD-1) and its ligand (PD-L1) in patients with NB. We found that PD-L1-expressing CD8+ T and NK cells in NB tumors were highly activated and functionally competent and associated with better clinical outcomes. Intratumoral NK cells were a favorable prognostic biomarker independent of CD8+ T cells, PD-1/PD-L1 expression, tumor stage, MYCN amplification, and risk classification. NK cells combined with anti-PD-1/PD-L1 antibodies showed potent antitumor activity against both MYCN-amplified and non-amplified NBs in vitro and in vivo, and PD-L1-expressing NK cells associated with improved antitumor efficacy. Collectively, we raise novel insights into the role of PD-L1 expression on CD8+ T-cell and NK-cell activation. We highlight the great potential of intratumoral NK cells in better defining risk stratification, and predicting survival and response to anti-PD-1/PD-L1 therapy in NB. These findings explain why single anti-PD-1/PD-L1 therapy may not be successful in NB, suggesting its combination with NK cell-adoptive cellular therapy as a promising strategy for relapsing/refractory NB. This study provides a potential prospect that patients with PD-L1-expressing NK cells may respond to anti-PD-1/PD-L1 therapy.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2289738Immunotherapynatural killer cellsneuroblastomaprogrammed death ligand 1 |
| spellingShingle | Mengjia Song Yue Huang Ye Hong Juan Liu Jia Zhu Suying Lu Juan Wang Feifei Sun Junting Huang Jiaqian Xu Yan Tang Jian-Chuan Xia Yizhuo Zhang PD-L1-expressing natural killer cells predict favorable prognosis and response to PD-1/PD-L1 blockade in neuroblastoma OncoImmunology Immunotherapy natural killer cells neuroblastoma programmed death ligand 1 |
| title | PD-L1-expressing natural killer cells predict favorable prognosis and response to PD-1/PD-L1 blockade in neuroblastoma |
| title_full | PD-L1-expressing natural killer cells predict favorable prognosis and response to PD-1/PD-L1 blockade in neuroblastoma |
| title_fullStr | PD-L1-expressing natural killer cells predict favorable prognosis and response to PD-1/PD-L1 blockade in neuroblastoma |
| title_full_unstemmed | PD-L1-expressing natural killer cells predict favorable prognosis and response to PD-1/PD-L1 blockade in neuroblastoma |
| title_short | PD-L1-expressing natural killer cells predict favorable prognosis and response to PD-1/PD-L1 blockade in neuroblastoma |
| title_sort | pd l1 expressing natural killer cells predict favorable prognosis and response to pd 1 pd l1 blockade in neuroblastoma |
| topic | Immunotherapy natural killer cells neuroblastoma programmed death ligand 1 |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2289738 |
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