Alternative splicing of modulatory immune receptors in T lymphocytes: a newly identified and targetable mechanism for anticancer immunotherapy
Alternative splicing (AS) is a mechanism that generates translational diversity within a genome. Equally important is the dynamic adaptability of the splicing machinery, which can give preference to one isoform over others encoded by a single gene. These isoform preferences change in response to the...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1490035/full |
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| author | Shay Tzaban Ori Stern Elad Zisman Galit Eisenberg Galit Eisenberg Shiri Klein Shiri Klein Shoshana Frankenburg Michal Lotem Michal Lotem Michal Lotem |
| author_facet | Shay Tzaban Ori Stern Elad Zisman Galit Eisenberg Galit Eisenberg Shiri Klein Shiri Klein Shoshana Frankenburg Michal Lotem Michal Lotem Michal Lotem |
| author_sort | Shay Tzaban |
| collection | DOAJ |
| description | Alternative splicing (AS) is a mechanism that generates translational diversity within a genome. Equally important is the dynamic adaptability of the splicing machinery, which can give preference to one isoform over others encoded by a single gene. These isoform preferences change in response to the cell’s state and function. Particularly significant is the impact of physiological alternative splicing in T lymphocytes, where specific isoforms can enhance or reduce the cells’ reactivity to stimuli. This process makes splicing isoforms defining features of cell states, exemplified by CD45 splice isoforms, which characterize the transition from naïve to memory states. Two developments have accelerated the use of AS dynamics for therapeutic interventions: advancements in long-read RNA sequencing and progress in nucleic acid chemical modifications. Improved oligonucleotide stability has enabled their use in directing splicing to specific sites or modifying sequences to enhance or silence particular splicing events. This review highlights immune regulatory splicing patterns with potential significance for enhancing anticancer immunotherapy. |
| format | Article |
| id | doaj-art-a0ab20c525ff4c7daddf03b22bf9de02 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-a0ab20c525ff4c7daddf03b22bf9de022025-01-07T06:40:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14900351490035Alternative splicing of modulatory immune receptors in T lymphocytes: a newly identified and targetable mechanism for anticancer immunotherapyShay Tzaban0Ori Stern1Elad Zisman2Galit Eisenberg3Galit Eisenberg4Shiri Klein5Shiri Klein6Shoshana Frankenburg7Michal Lotem8Michal Lotem9Michal Lotem10The Lautenberg Center for Immunology and Cancer Research, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelThe Lautenberg Center for Immunology and Cancer Research, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelThe Lautenberg Center for Immunology and Cancer Research, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelThe Lautenberg Center for Immunology and Cancer Research, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelCenter for Melanoma and Cancer Immunotherapy, Sharett Institute of Oncology, Jerusalem, IsraelThe Lautenberg Center for Immunology and Cancer Research, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelCenter for Melanoma and Cancer Immunotherapy, Sharett Institute of Oncology, Jerusalem, IsraelThe Lautenberg Center for Immunology and Cancer Research, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelThe Lautenberg Center for Immunology and Cancer Research, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelCenter for Melanoma and Cancer Immunotherapy, Sharett Institute of Oncology, Jerusalem, IsraelHadassah Cancer Research Institute, Hadassah Hebrew University Medical Center, Jerusalem, IsraelAlternative splicing (AS) is a mechanism that generates translational diversity within a genome. Equally important is the dynamic adaptability of the splicing machinery, which can give preference to one isoform over others encoded by a single gene. These isoform preferences change in response to the cell’s state and function. Particularly significant is the impact of physiological alternative splicing in T lymphocytes, where specific isoforms can enhance or reduce the cells’ reactivity to stimuli. This process makes splicing isoforms defining features of cell states, exemplified by CD45 splice isoforms, which characterize the transition from naïve to memory states. Two developments have accelerated the use of AS dynamics for therapeutic interventions: advancements in long-read RNA sequencing and progress in nucleic acid chemical modifications. Improved oligonucleotide stability has enabled their use in directing splicing to specific sites or modifying sequences to enhance or silence particular splicing events. This review highlights immune regulatory splicing patterns with potential significance for enhancing anticancer immunotherapy.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1490035/fullalternative splicingcancerimmunotherapyT lymphocytesimmune receptors |
| spellingShingle | Shay Tzaban Ori Stern Elad Zisman Galit Eisenberg Galit Eisenberg Shiri Klein Shiri Klein Shoshana Frankenburg Michal Lotem Michal Lotem Michal Lotem Alternative splicing of modulatory immune receptors in T lymphocytes: a newly identified and targetable mechanism for anticancer immunotherapy Frontiers in Immunology alternative splicing cancer immunotherapy T lymphocytes immune receptors |
| title | Alternative splicing of modulatory immune receptors in T lymphocytes: a newly identified and targetable mechanism for anticancer immunotherapy |
| title_full | Alternative splicing of modulatory immune receptors in T lymphocytes: a newly identified and targetable mechanism for anticancer immunotherapy |
| title_fullStr | Alternative splicing of modulatory immune receptors in T lymphocytes: a newly identified and targetable mechanism for anticancer immunotherapy |
| title_full_unstemmed | Alternative splicing of modulatory immune receptors in T lymphocytes: a newly identified and targetable mechanism for anticancer immunotherapy |
| title_short | Alternative splicing of modulatory immune receptors in T lymphocytes: a newly identified and targetable mechanism for anticancer immunotherapy |
| title_sort | alternative splicing of modulatory immune receptors in t lymphocytes a newly identified and targetable mechanism for anticancer immunotherapy |
| topic | alternative splicing cancer immunotherapy T lymphocytes immune receptors |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1490035/full |
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