Endogenous CCL21-Ser deficiency reduces B16–F10 melanoma growth by enhanced antitumor immunity
The chemokine CCL21 regulates immune and cancer cell migration through its receptor CCR7. The Ccl21a gene encodes the isoform CCL21-Ser, predominantly expressed in the thymic medulla and the secondary lymphoid tissues. This study examined the roles of CCL21-Ser in the antitumor immune response in Cc...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402306423X |
| _version_ | 1827856077484457984 |
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| author | Ryonosuke Fujie Kaoru Kurowarabe Yuki Yamada Kakeru Fujiwara Hayato Nakatani Kenta Tsutsumi Ryota Hayashi Hinami Kawahata Megumi Miyamoto Madoka Ozawa Tomoya Katakai Yousuke Takahama Izumi Ohigashi Haruko Hayasaka |
| author_facet | Ryonosuke Fujie Kaoru Kurowarabe Yuki Yamada Kakeru Fujiwara Hayato Nakatani Kenta Tsutsumi Ryota Hayashi Hinami Kawahata Megumi Miyamoto Madoka Ozawa Tomoya Katakai Yousuke Takahama Izumi Ohigashi Haruko Hayasaka |
| author_sort | Ryonosuke Fujie |
| collection | DOAJ |
| description | The chemokine CCL21 regulates immune and cancer cell migration through its receptor CCR7. The Ccl21a gene encodes the isoform CCL21-Ser, predominantly expressed in the thymic medulla and the secondary lymphoid tissues. This study examined the roles of CCL21-Ser in the antitumor immune response in Ccl21a-knockout (KO) mice. The Ccl21a-KO mice showed significantly decreased growth of B16–F10 and YUMM1.7 melanomas and increased growth of MC38 colon cancer, despite no significant difference in LLC lung cancer and EO771 breast cancer. The B16–F10 tumor in Ccl21a-KO mice showed melanoma-specific activated CD8+ T cell and NK cell infiltration and higher Treg counts than wild-type mice. B16–F10 tumors in Ccl21a-KO mice showed a reduction in the positive correlation between the ratio of regulatory T cells (Tregs) to activated CD8+ T cells and tumor weight. In Ccl21a-KO tumor, the intratumoral Tregs showed lower co-inhibitory receptors TIM-3 and TIGIT. Taken together, these results suggest that endogenous CCL21-Ser supports melanoma growth in vivo by maintaining Treg function and suppressing antitumor immunity by CD8+ T cells. |
| first_indexed | 2024-03-12T12:20:33Z |
| format | Article |
| id | doaj.art-534acb27c84d470f9741f98656fdfbca |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-12T12:20:33Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-534acb27c84d470f9741f98656fdfbca2023-08-30T05:54:01ZengElsevierHeliyon2405-84402023-08-0198e19215Endogenous CCL21-Ser deficiency reduces B16–F10 melanoma growth by enhanced antitumor immunityRyonosuke Fujie0Kaoru Kurowarabe1Yuki Yamada2Kakeru Fujiwara3Hayato Nakatani4Kenta Tsutsumi5Ryota Hayashi6Hinami Kawahata7Megumi Miyamoto8Madoka Ozawa9Tomoya Katakai10Yousuke Takahama11Izumi Ohigashi12Haruko Hayasaka13Department of Science, Graduate School of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, JapanDepartment of Science, Graduate School of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, JapanFaculty of Science & Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, JapanDepartment of Science, Graduate School of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, JapanFaculty of Science & Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, JapanFaculty of Science & Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, JapanDepartment of Science, Graduate School of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, JapanFaculty of Science & Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, JapanDepartment of Science, Graduate School of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, JapanDepartment of Immunology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, JapanDepartment of Immunology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, JapanDivision of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, Japan; Thymus Biology Section, Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United StatesDivision of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, JapanDepartment of Science, Graduate School of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan; Faculty of Science & Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan; Research Institute for Science and Technology, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan; Corresponding author. Department of Science, Graduate School of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.The chemokine CCL21 regulates immune and cancer cell migration through its receptor CCR7. The Ccl21a gene encodes the isoform CCL21-Ser, predominantly expressed in the thymic medulla and the secondary lymphoid tissues. This study examined the roles of CCL21-Ser in the antitumor immune response in Ccl21a-knockout (KO) mice. The Ccl21a-KO mice showed significantly decreased growth of B16–F10 and YUMM1.7 melanomas and increased growth of MC38 colon cancer, despite no significant difference in LLC lung cancer and EO771 breast cancer. The B16–F10 tumor in Ccl21a-KO mice showed melanoma-specific activated CD8+ T cell and NK cell infiltration and higher Treg counts than wild-type mice. B16–F10 tumors in Ccl21a-KO mice showed a reduction in the positive correlation between the ratio of regulatory T cells (Tregs) to activated CD8+ T cells and tumor weight. In Ccl21a-KO tumor, the intratumoral Tregs showed lower co-inhibitory receptors TIM-3 and TIGIT. Taken together, these results suggest that endogenous CCL21-Ser supports melanoma growth in vivo by maintaining Treg function and suppressing antitumor immunity by CD8+ T cells.http://www.sciencedirect.com/science/article/pii/S240584402306423XMelanomaChemokineLymph nodeCD8Treg |
| spellingShingle | Ryonosuke Fujie Kaoru Kurowarabe Yuki Yamada Kakeru Fujiwara Hayato Nakatani Kenta Tsutsumi Ryota Hayashi Hinami Kawahata Megumi Miyamoto Madoka Ozawa Tomoya Katakai Yousuke Takahama Izumi Ohigashi Haruko Hayasaka Endogenous CCL21-Ser deficiency reduces B16–F10 melanoma growth by enhanced antitumor immunity Heliyon Melanoma Chemokine Lymph node CD8 Treg |
| title | Endogenous CCL21-Ser deficiency reduces B16–F10 melanoma growth by enhanced antitumor immunity |
| title_full | Endogenous CCL21-Ser deficiency reduces B16–F10 melanoma growth by enhanced antitumor immunity |
| title_fullStr | Endogenous CCL21-Ser deficiency reduces B16–F10 melanoma growth by enhanced antitumor immunity |
| title_full_unstemmed | Endogenous CCL21-Ser deficiency reduces B16–F10 melanoma growth by enhanced antitumor immunity |
| title_short | Endogenous CCL21-Ser deficiency reduces B16–F10 melanoma growth by enhanced antitumor immunity |
| title_sort | endogenous ccl21 ser deficiency reduces b16 f10 melanoma growth by enhanced antitumor immunity |
| topic | Melanoma Chemokine Lymph node CD8 Treg |
| url | http://www.sciencedirect.com/science/article/pii/S240584402306423X |
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