Anti-PD-1 antibody enhances homeostatic proliferation–induced antitumor immunity during lymphopenia recovery
IntroductionLymphopenia induced by radiotherapy or chemotherapy can promote homeostatic proliferation of residual or adoptive lymphocytes, potentially enhancing antitumor immunity. However, this immunity diminishes rapidly with tumor progression, and the underlying mechanisms remain unclear. This st...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1563894/full |
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| author | Zike Yang Ying Zhu Qian Wang Qing Lin Yahui Liu |
| author_facet | Zike Yang Ying Zhu Qian Wang Qing Lin Yahui Liu |
| author_sort | Zike Yang |
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| description | IntroductionLymphopenia induced by radiotherapy or chemotherapy can promote homeostatic proliferation of residual or adoptive lymphocytes, potentially enhancing antitumor immunity. However, this immunity diminishes rapidly with tumor progression, and the underlying mechanisms remain unclear. This study investigates the role of PD-1 signaling in homeostatic proliferation–induced antitumor immunity in malignant melanoma.MethodsWe evaluated T-cell dynamics in lymphopenic mice, analyzing PD-1 expression, IFN-γ production by CD8+ T cells, and T-cell cytotoxicity during homeostatic proliferation. The PD-1/PD-L1 axis was blocked using anti-PD-1 antibodies to assess its impact on T-cell function, dendritic cell (DC) activation, and memory T-cell differentiation.ResultsAlthough T cells proliferated continuously in lymphopenic mice, IFN-γ+ CD8+ T cells declined over time. PD-1 expression on T cells increased progressively and correlated negatively with effector T-cell cytotoxicity. PD-1 blockade enhanced the recognition of tumor-associated antigens (TAAs) by homeostatically proliferating (HP) T cells, activated DCs, and increased IFN-γ+ CD8+ T-cell numbers. Additionally, it boosted T-cell cytotoxicity and promoted the conversion of tumor-specific effector T cells into central memory T cells.DiscussionThese findings indicate that the PD-1/PD-L1 axis plays a critical role in immune tolerance during homeostatic proliferation. Anti-PD-1 therapy may enhance antitumor immunity during lymphopenia recovery after chemotherapy or radiotherapy, offering a potential strategy to sustain T-cell–mediated tumor control. |
| format | Article |
| id | doaj-art-978191e8665f47759deeef37e5661fae |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-978191e8665f47759deeef37e5661fae2025-08-20T03:51:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.15638941563894Anti-PD-1 antibody enhances homeostatic proliferation–induced antitumor immunity during lymphopenia recoveryZike Yang0Ying Zhu1Qian Wang2Qing Lin3Yahui Liu4Department of Oncology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, ChinaDepartment of Obstetrics and Gynecology, The Third Affiliated Hospital/The Third Clinical Medicine School of Southern Medical University, Guangzhou, ChinaDepartment of Obstetrics and Gynecology, The Third Affiliated Hospital/The Third Clinical Medicine School of Southern Medical University, Guangzhou, ChinaDepartment of Rehabilitation, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, ChinaDepartment of Oncology, Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, ChinaIntroductionLymphopenia induced by radiotherapy or chemotherapy can promote homeostatic proliferation of residual or adoptive lymphocytes, potentially enhancing antitumor immunity. However, this immunity diminishes rapidly with tumor progression, and the underlying mechanisms remain unclear. This study investigates the role of PD-1 signaling in homeostatic proliferation–induced antitumor immunity in malignant melanoma.MethodsWe evaluated T-cell dynamics in lymphopenic mice, analyzing PD-1 expression, IFN-γ production by CD8+ T cells, and T-cell cytotoxicity during homeostatic proliferation. The PD-1/PD-L1 axis was blocked using anti-PD-1 antibodies to assess its impact on T-cell function, dendritic cell (DC) activation, and memory T-cell differentiation.ResultsAlthough T cells proliferated continuously in lymphopenic mice, IFN-γ+ CD8+ T cells declined over time. PD-1 expression on T cells increased progressively and correlated negatively with effector T-cell cytotoxicity. PD-1 blockade enhanced the recognition of tumor-associated antigens (TAAs) by homeostatically proliferating (HP) T cells, activated DCs, and increased IFN-γ+ CD8+ T-cell numbers. Additionally, it boosted T-cell cytotoxicity and promoted the conversion of tumor-specific effector T cells into central memory T cells.DiscussionThese findings indicate that the PD-1/PD-L1 axis plays a critical role in immune tolerance during homeostatic proliferation. Anti-PD-1 therapy may enhance antitumor immunity during lymphopenia recovery after chemotherapy or radiotherapy, offering a potential strategy to sustain T-cell–mediated tumor control.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1563894/fullPD-1/PD-L1lymphopeniaimmunotherapymelanomahomeostatic proliferationantitumor immunity |
| spellingShingle | Zike Yang Ying Zhu Qian Wang Qing Lin Yahui Liu Anti-PD-1 antibody enhances homeostatic proliferation–induced antitumor immunity during lymphopenia recovery Frontiers in Immunology PD-1/PD-L1 lymphopenia immunotherapy melanoma homeostatic proliferation antitumor immunity |
| title | Anti-PD-1 antibody enhances homeostatic proliferation–induced antitumor immunity during lymphopenia recovery |
| title_full | Anti-PD-1 antibody enhances homeostatic proliferation–induced antitumor immunity during lymphopenia recovery |
| title_fullStr | Anti-PD-1 antibody enhances homeostatic proliferation–induced antitumor immunity during lymphopenia recovery |
| title_full_unstemmed | Anti-PD-1 antibody enhances homeostatic proliferation–induced antitumor immunity during lymphopenia recovery |
| title_short | Anti-PD-1 antibody enhances homeostatic proliferation–induced antitumor immunity during lymphopenia recovery |
| title_sort | anti pd 1 antibody enhances homeostatic proliferation induced antitumor immunity during lymphopenia recovery |
| topic | PD-1/PD-L1 lymphopenia immunotherapy melanoma homeostatic proliferation antitumor immunity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1563894/full |
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