Revealing the mechanisms and therapeutic potential of immune checkpoint proteins across diverse protein families
Host immune responses to antigens are tightly regulated through the activation and inhibition of synergistic signaling networks that maintain homeostasis. Stimulatory checkpoint molecules initiate attacks on infected or tumor cells, while inhibitory molecules halt the immune response to prevent over...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1499663/full |
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| author | Ran Liu Xinyan Jiang Ruijuan Dong Yuting Zhang Cong Gai Peng Wei |
| author_facet | Ran Liu Xinyan Jiang Ruijuan Dong Yuting Zhang Cong Gai Peng Wei |
| author_sort | Ran Liu |
| collection | DOAJ |
| description | Host immune responses to antigens are tightly regulated through the activation and inhibition of synergistic signaling networks that maintain homeostasis. Stimulatory checkpoint molecules initiate attacks on infected or tumor cells, while inhibitory molecules halt the immune response to prevent overreaction and self-injury. Multiple immune checkpoint proteins are grouped into families based on common structural domains or origins, yet the variability within and between these families remains largely unexplored. In this review, we discuss the current understanding of the mechanisms underlying the co-suppressive functions of CTLA-4, PD-1, and other prominent immune checkpoint pathways. Additionally, we examine the IgSF, PVR, TIM, SIRP, and TNF families, including key members such as TIGIT, LAG-3, VISTA, TIM-3, SIRPα, and OX40. We also highlight the unique dual role of VISTA and SIRPα in modulating immune responses under specific conditions, and explore potential immunotherapeutic pathways tailored to the distinct characteristics of different immune checkpoint proteins. These insights into the unique advantages of checkpoint proteins provide new directions for drug discovery, emphasizing that emerging immune checkpoint molecules could serve as targets for novel therapies in cancer, autoimmune diseases, infectious diseases, and transplant rejection. |
| format | Article |
| id | doaj-art-7138383af8d54dbdaa17ea9a38ccfaf2 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-7138383af8d54dbdaa17ea9a38ccfaf22025-08-20T02:19:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.14996631499663Revealing the mechanisms and therapeutic potential of immune checkpoint proteins across diverse protein familiesRan LiuXinyan JiangRuijuan DongYuting ZhangCong GaiPeng WeiHost immune responses to antigens are tightly regulated through the activation and inhibition of synergistic signaling networks that maintain homeostasis. Stimulatory checkpoint molecules initiate attacks on infected or tumor cells, while inhibitory molecules halt the immune response to prevent overreaction and self-injury. Multiple immune checkpoint proteins are grouped into families based on common structural domains or origins, yet the variability within and between these families remains largely unexplored. In this review, we discuss the current understanding of the mechanisms underlying the co-suppressive functions of CTLA-4, PD-1, and other prominent immune checkpoint pathways. Additionally, we examine the IgSF, PVR, TIM, SIRP, and TNF families, including key members such as TIGIT, LAG-3, VISTA, TIM-3, SIRPα, and OX40. We also highlight the unique dual role of VISTA and SIRPα in modulating immune responses under specific conditions, and explore potential immunotherapeutic pathways tailored to the distinct characteristics of different immune checkpoint proteins. These insights into the unique advantages of checkpoint proteins provide new directions for drug discovery, emphasizing that emerging immune checkpoint molecules could serve as targets for novel therapies in cancer, autoimmune diseases, infectious diseases, and transplant rejection.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1499663/fullimmunotherapyimmune checkpoint proteinstumor microenvironment specificityco-suppressive pathwaysprotein families |
| spellingShingle | Ran Liu Xinyan Jiang Ruijuan Dong Yuting Zhang Cong Gai Peng Wei Revealing the mechanisms and therapeutic potential of immune checkpoint proteins across diverse protein families Frontiers in Immunology immunotherapy immune checkpoint proteins tumor microenvironment specificity co-suppressive pathways protein families |
| title | Revealing the mechanisms and therapeutic potential of immune checkpoint proteins across diverse protein families |
| title_full | Revealing the mechanisms and therapeutic potential of immune checkpoint proteins across diverse protein families |
| title_fullStr | Revealing the mechanisms and therapeutic potential of immune checkpoint proteins across diverse protein families |
| title_full_unstemmed | Revealing the mechanisms and therapeutic potential of immune checkpoint proteins across diverse protein families |
| title_short | Revealing the mechanisms and therapeutic potential of immune checkpoint proteins across diverse protein families |
| title_sort | revealing the mechanisms and therapeutic potential of immune checkpoint proteins across diverse protein families |
| topic | immunotherapy immune checkpoint proteins tumor microenvironment specificity co-suppressive pathways protein families |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1499663/full |
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