Alternative splicing: A key regulator in T cell response and cancer immunotherapy
Alternative splicing (AS), a key post-transcriptional regulatory mechanism, is frequently dysregulated in cancer, driving both tumor progression and immune modulation. Aberrant AS influences antigen presentation, T cell activation, immune checkpoint regulation, and cytokine signaling, contributing t...
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Elsevier
2025-05-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825001380 |
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| author | Caiyu Yong Yexin Liang Minmin Wang Weiwei Jin Xuefei Fan Zhengwen Wang Kui Cao Tong Wu Qian Li Cunjie Chang |
| author_facet | Caiyu Yong Yexin Liang Minmin Wang Weiwei Jin Xuefei Fan Zhengwen Wang Kui Cao Tong Wu Qian Li Cunjie Chang |
| author_sort | Caiyu Yong |
| collection | DOAJ |
| description | Alternative splicing (AS), a key post-transcriptional regulatory mechanism, is frequently dysregulated in cancer, driving both tumor progression and immune modulation. Aberrant AS influences antigen presentation, T cell activation, immune checkpoint regulation, and cytokine signaling, contributing to immune evasion but also presenting unique therapeutic vulnerabilities. Targeting AS has emerged as a promising strategy in cancer immunotherapy. Splicing-derived neoantigens have been identified as potent inducers of CD8⁺ T cell responses, offering potential for personalized treatment. AS modulators such as PRMT5 inhibitor GSK3326595 enhance immunotherapy efficacy by upregulating MHC class II expression and promoting T cell infiltration, while RBM39 inhibitor indisulam induces tumor-specific neoantigens. Furthermore, combining AS-targeting drugs with immune checkpoint inhibitors (ICIs) has demonstrated synergistic effects, improved response rates and overcoming resistance in preclinical models. Despite these advances, challenges remain in optimizing drug specificity and minimizing toxicity. Future efforts should focus on refining AS-targeting therapies, identifying predictive biomarkers, and integrating these approaches into clinical applications. This review highlights the therapeutic potential of AS modulation in cancer immunotherapy and its implications for advancing precision oncology. |
| format | Article |
| id | doaj-art-6c67eb19de844cfab25063f3d9fea4fe |
| institution | OA Journals |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-6c67eb19de844cfab25063f3d9fea4fe2025-08-20T02:18:55ZengElsevierPharmacological Research1096-11862025-05-0121510771310.1016/j.phrs.2025.107713Alternative splicing: A key regulator in T cell response and cancer immunotherapyCaiyu Yong0Yexin Liang1Minmin Wang2Weiwei Jin3Xuefei Fan4Zhengwen Wang5Kui Cao6Tong Wu7Qian Li8Cunjie Chang9School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR ChinaSchool of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR ChinaSchool of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR ChinaSchool of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR ChinaSchool of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR ChinaSchool of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR ChinaSchool of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR ChinaSchool of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR ChinaSchool of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR ChinaSchool of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR China; Corresponding author at: School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, PR China.Alternative splicing (AS), a key post-transcriptional regulatory mechanism, is frequently dysregulated in cancer, driving both tumor progression and immune modulation. Aberrant AS influences antigen presentation, T cell activation, immune checkpoint regulation, and cytokine signaling, contributing to immune evasion but also presenting unique therapeutic vulnerabilities. Targeting AS has emerged as a promising strategy in cancer immunotherapy. Splicing-derived neoantigens have been identified as potent inducers of CD8⁺ T cell responses, offering potential for personalized treatment. AS modulators such as PRMT5 inhibitor GSK3326595 enhance immunotherapy efficacy by upregulating MHC class II expression and promoting T cell infiltration, while RBM39 inhibitor indisulam induces tumor-specific neoantigens. Furthermore, combining AS-targeting drugs with immune checkpoint inhibitors (ICIs) has demonstrated synergistic effects, improved response rates and overcoming resistance in preclinical models. Despite these advances, challenges remain in optimizing drug specificity and minimizing toxicity. Future efforts should focus on refining AS-targeting therapies, identifying predictive biomarkers, and integrating these approaches into clinical applications. This review highlights the therapeutic potential of AS modulation in cancer immunotherapy and its implications for advancing precision oncology.http://www.sciencedirect.com/science/article/pii/S1043661825001380Alternative splicingNeoantigenT-cell responseImmunotherapy |
| spellingShingle | Caiyu Yong Yexin Liang Minmin Wang Weiwei Jin Xuefei Fan Zhengwen Wang Kui Cao Tong Wu Qian Li Cunjie Chang Alternative splicing: A key regulator in T cell response and cancer immunotherapy Pharmacological Research Alternative splicing Neoantigen T-cell response Immunotherapy |
| title | Alternative splicing: A key regulator in T cell response and cancer immunotherapy |
| title_full | Alternative splicing: A key regulator in T cell response and cancer immunotherapy |
| title_fullStr | Alternative splicing: A key regulator in T cell response and cancer immunotherapy |
| title_full_unstemmed | Alternative splicing: A key regulator in T cell response and cancer immunotherapy |
| title_short | Alternative splicing: A key regulator in T cell response and cancer immunotherapy |
| title_sort | alternative splicing a key regulator in t cell response and cancer immunotherapy |
| topic | Alternative splicing Neoantigen T-cell response Immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825001380 |
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