Department of Science, Graduate School of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan
Kaoru Kurowarabe
Department of Science, Graduate School of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan
Yuki Yamada
Faculty of Science & Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan
Kakeru Fujiwara
Department of Science, Graduate School of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan
Hayato Nakatani
Faculty of Science & Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan
Kenta Tsutsumi
Faculty of Science & Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan
Ryota Hayashi
Department of Science, Graduate School of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan
Hinami Kawahata
Faculty of Science & Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan
Megumi Miyamoto
Department of Science, Graduate School of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan
Madoka Ozawa
Department of Immunology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan
Tomoya Katakai
Department of Immunology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan
Yousuke Takahama
Division 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 States
Izumi Ohigashi
Division of Experimental Immunology, Institute of Advanced Medical Sciences, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, Japan
Haruko Hayasaka
Department 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.
