LFA-1 regulated by IL-2/STAT5 pathway boosts antitumor function of intratumoral CD8+ T cells for improving anti-PD-1 antibody therapy
Anti-PD-1 antibody therapy has achieved success in tumor treatment; however, the duration of its clinical benefits are typically short. The functional state of intratumoral CD8+ T cells substantially affects the efficacy of anti-PD-1 antibody therapy. Understanding how intratumoral CD8+ T cells chan...
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| Format: | Article |
| Language: | English |
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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.2023.2293511 |
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| author | Jiqi Shan Wei Jing Yu Ping Chunyi Shen Dong Han Fengsen Liu Yaqing Liu Congcong Li Yi Zhang |
| author_facet | Jiqi Shan Wei Jing Yu Ping Chunyi Shen Dong Han Fengsen Liu Yaqing Liu Congcong Li Yi Zhang |
| author_sort | Jiqi Shan |
| collection | DOAJ |
| description | Anti-PD-1 antibody therapy has achieved success in tumor treatment; however, the duration of its clinical benefits are typically short. The functional state of intratumoral CD8+ T cells substantially affects the efficacy of anti-PD-1 antibody therapy. Understanding how intratumoral CD8+ T cells change will contribute to the improvement in anti-PD-1 antibody therapy. In this study, we found that tumor growth was not arrested after the late administration of anti-PD-1 antibody and that the antitumor function of CD8+ T cells decreased with tumor progression. The results of the RNA sequencing of CD8+ T cells infiltrating the tumor site on days 7 and 14 showed that the cell adhesion molecule Lymphocyte Function-associated Antigen-1 (LFA-1) participates in regulating the antitumor function of CD8+ T cells and that decreased LFA-1 expression in intratumoral CD8+ T cells is associated with tumor progression. By analyzing the Gene Expression Omnibus (GEO) database and our results, we found that the antitumor function of intratumoral CD8+ T cells with high LFA-1 expression was stronger. The formation of immune synapses is impaired in Itgal-si CD8+ T cells, resulting in decreased anti-tumor function. LFA-1 expression in intratumoral CD8+ T cells is regulated by the IL-2/STAT5 pathway. The combination of IL-2 and anti-PD-1 antibody effectively enhanced LFA-1 expression and the antitumor function of intratumoral CD8+ T cells. The adoptive transfer of OT-1 T cells overexpressing LFA-1, STAT5A, or STAT5B resulted in higher antitumor function, deferred tumor growth, and prolonged survival. These findings indicate that LFA-1-mediated immune synapse acts as a regulator of the antitumor function of intratumoral CD8+ T cells, which can be applied to improve anti-PD-1 antibody therapy. |
| format | Article |
| id | doaj-art-40929eb3d9084be095904ba4d74e9276 |
| institution | DOAJ |
| issn | 2162-402X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-40929eb3d9084be095904ba4d74e92762025-08-20T02:50:37ZengTaylor & Francis GroupOncoImmunology2162-402X2024-12-0113110.1080/2162402X.2023.2293511LFA-1 regulated by IL-2/STAT5 pathway boosts antitumor function of intratumoral CD8+ T cells for improving anti-PD-1 antibody therapyJiqi Shan0Wei Jing1Yu Ping2Chunyi Shen3Dong Han4Fengsen Liu5Yaqing Liu6Congcong Li7Yi Zhang8Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaBiotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaBiotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaBiotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaBiotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaBiotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaBiotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaBiotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaBiotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaAnti-PD-1 antibody therapy has achieved success in tumor treatment; however, the duration of its clinical benefits are typically short. The functional state of intratumoral CD8+ T cells substantially affects the efficacy of anti-PD-1 antibody therapy. Understanding how intratumoral CD8+ T cells change will contribute to the improvement in anti-PD-1 antibody therapy. In this study, we found that tumor growth was not arrested after the late administration of anti-PD-1 antibody and that the antitumor function of CD8+ T cells decreased with tumor progression. The results of the RNA sequencing of CD8+ T cells infiltrating the tumor site on days 7 and 14 showed that the cell adhesion molecule Lymphocyte Function-associated Antigen-1 (LFA-1) participates in regulating the antitumor function of CD8+ T cells and that decreased LFA-1 expression in intratumoral CD8+ T cells is associated with tumor progression. By analyzing the Gene Expression Omnibus (GEO) database and our results, we found that the antitumor function of intratumoral CD8+ T cells with high LFA-1 expression was stronger. The formation of immune synapses is impaired in Itgal-si CD8+ T cells, resulting in decreased anti-tumor function. LFA-1 expression in intratumoral CD8+ T cells is regulated by the IL-2/STAT5 pathway. The combination of IL-2 and anti-PD-1 antibody effectively enhanced LFA-1 expression and the antitumor function of intratumoral CD8+ T cells. The adoptive transfer of OT-1 T cells overexpressing LFA-1, STAT5A, or STAT5B resulted in higher antitumor function, deferred tumor growth, and prolonged survival. These findings indicate that LFA-1-mediated immune synapse acts as a regulator of the antitumor function of intratumoral CD8+ T cells, which can be applied to improve anti-PD-1 antibody therapy.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2293511CD8+ T cellsLFA-1immune synapseIL-2anti-tumor functionAnti-PD-1 antibody |
| spellingShingle | Jiqi Shan Wei Jing Yu Ping Chunyi Shen Dong Han Fengsen Liu Yaqing Liu Congcong Li Yi Zhang LFA-1 regulated by IL-2/STAT5 pathway boosts antitumor function of intratumoral CD8+ T cells for improving anti-PD-1 antibody therapy OncoImmunology CD8+ T cells LFA-1 immune synapse IL-2 anti-tumor function Anti-PD-1 antibody |
| title | LFA-1 regulated by IL-2/STAT5 pathway boosts antitumor function of intratumoral CD8+ T cells for improving anti-PD-1 antibody therapy |
| title_full | LFA-1 regulated by IL-2/STAT5 pathway boosts antitumor function of intratumoral CD8+ T cells for improving anti-PD-1 antibody therapy |
| title_fullStr | LFA-1 regulated by IL-2/STAT5 pathway boosts antitumor function of intratumoral CD8+ T cells for improving anti-PD-1 antibody therapy |
| title_full_unstemmed | LFA-1 regulated by IL-2/STAT5 pathway boosts antitumor function of intratumoral CD8+ T cells for improving anti-PD-1 antibody therapy |
| title_short | LFA-1 regulated by IL-2/STAT5 pathway boosts antitumor function of intratumoral CD8+ T cells for improving anti-PD-1 antibody therapy |
| title_sort | lfa 1 regulated by il 2 stat5 pathway boosts antitumor function of intratumoral cd8 t cells for improving anti pd 1 antibody therapy |
| topic | CD8+ T cells LFA-1 immune synapse IL-2 anti-tumor function Anti-PD-1 antibody |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2293511 |
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