IL-18-primed NK cells recruit dendritic cells and potentiate tumor therapy mediated by PD-1 blockade
The success of cancer immunotherapy depends on the effective coordination of innate and adaptive immunity. We previously reported that IL-18 potentiates the therapeutic effects of immune checkpoint inhibitors in mouse models. Here, we report that IL-18-primed natural killer (NK) cells enhanced the a...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1533808/full |
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| author | Yoshiya Ohno Haruki Okamura Hideo Yagita Toshiyuki Tanaka |
| author_facet | Yoshiya Ohno Haruki Okamura Hideo Yagita Toshiyuki Tanaka |
| author_sort | Yoshiya Ohno |
| collection | DOAJ |
| description | The success of cancer immunotherapy depends on the effective coordination of innate and adaptive immunity. We previously reported that IL-18 potentiates the therapeutic effects of immune checkpoint inhibitors in mouse models. Here, we report that IL-18-primed natural killer (NK) cells enhanced the antitumor effects of anti-PD-1 antibodies by mobilizing type 1 conventional dendritic cells (cDC1s) to tumor sites and promoting type 1 immune responses. IL-18-primed NK cells had a premature phenotype, and expressed chemokines involved in cDC1 mobilization. In a combination treatment with IL-18 and anti-PD-1 antibody, NK cell depletion inhibited cDC1 mobilization and abrogated the therapeutic effects. Additionally, adoptive transfer of IL-18-primed NK cells induced cDC1 mobilization and enhanced the therapeutic effects of anti-PD-1 antibodies. IL-18 also increased IL-12 mRNA expression in DCs and IL-12 blood levels, and IL-12 upregulated XCL1 expression in NK cells. These results suggest that IL-18 primes NK cells and enhances the therapeutic effects of immune checkpoint inhibitors by promoting a feed-forward loop involving DCs. |
| format | Article |
| id | doaj-art-b9d92fcf75b64e2f9f57d7e4c7797b0b |
| institution | DOAJ |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-b9d92fcf75b64e2f9f57d7e4c7797b0b2025-08-20T03:01:26ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-03-011510.3389/fonc.2025.15338081533808IL-18-primed NK cells recruit dendritic cells and potentiate tumor therapy mediated by PD-1 blockadeYoshiya Ohno0Haruki Okamura1Hideo Yagita2Toshiyuki Tanaka3Laboratory of Immunobiology, School of Pharmacy, Hyogo Medical University, Kobe, Hyogo, JapanDepartment of Psychoimmunology, School of Medicine, Hyogo Medical University, Nishinomiya, Hyogo, JapanDepartment of Immunology, Juntendo University School of Medicine, Tokyo, JapanLaboratory of Immunobiology, School of Pharmacy, Hyogo Medical University, Kobe, Hyogo, JapanThe success of cancer immunotherapy depends on the effective coordination of innate and adaptive immunity. We previously reported that IL-18 potentiates the therapeutic effects of immune checkpoint inhibitors in mouse models. Here, we report that IL-18-primed natural killer (NK) cells enhanced the antitumor effects of anti-PD-1 antibodies by mobilizing type 1 conventional dendritic cells (cDC1s) to tumor sites and promoting type 1 immune responses. IL-18-primed NK cells had a premature phenotype, and expressed chemokines involved in cDC1 mobilization. In a combination treatment with IL-18 and anti-PD-1 antibody, NK cell depletion inhibited cDC1 mobilization and abrogated the therapeutic effects. Additionally, adoptive transfer of IL-18-primed NK cells induced cDC1 mobilization and enhanced the therapeutic effects of anti-PD-1 antibodies. IL-18 also increased IL-12 mRNA expression in DCs and IL-12 blood levels, and IL-12 upregulated XCL1 expression in NK cells. These results suggest that IL-18 primes NK cells and enhances the therapeutic effects of immune checkpoint inhibitors by promoting a feed-forward loop involving DCs.https://www.frontiersin.org/articles/10.3389/fonc.2025.1533808/fullIL-18immune checkpoint inhibitorPD-1NK cellscDC1 |
| spellingShingle | Yoshiya Ohno Haruki Okamura Hideo Yagita Toshiyuki Tanaka IL-18-primed NK cells recruit dendritic cells and potentiate tumor therapy mediated by PD-1 blockade Frontiers in Oncology IL-18 immune checkpoint inhibitor PD-1 NK cells cDC1 |
| title | IL-18-primed NK cells recruit dendritic cells and potentiate tumor therapy mediated by PD-1 blockade |
| title_full | IL-18-primed NK cells recruit dendritic cells and potentiate tumor therapy mediated by PD-1 blockade |
| title_fullStr | IL-18-primed NK cells recruit dendritic cells and potentiate tumor therapy mediated by PD-1 blockade |
| title_full_unstemmed | IL-18-primed NK cells recruit dendritic cells and potentiate tumor therapy mediated by PD-1 blockade |
| title_short | IL-18-primed NK cells recruit dendritic cells and potentiate tumor therapy mediated by PD-1 blockade |
| title_sort | il 18 primed nk cells recruit dendritic cells and potentiate tumor therapy mediated by pd 1 blockade |
| topic | IL-18 immune checkpoint inhibitor PD-1 NK cells cDC1 |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1533808/full |
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