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Updated: Jul 17, 2025
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Endogenous CCL21-Ser deficiency reduces B16-F10 melanoma growth by enhanced antitumor immunity
Ryonosuke Fujie1, Kaoru Kurowarabe1, Yuki Yamada2
1Department of Science, Graduate School of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
Abstract:
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.
Insights
Endogenous CCL21-Ser promotes melanoma growth by supporting regulatory T cell (Treg) function and suppressing CD8+ T cell antitumor immunity. CCL21-Ser knockout mice showed reduced melanoma growth and altered immune cell infiltration.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- Chemokine CCL21, via its receptor CCR7, controls immune and cancer cell movement.
- CCL21-Ser, encoded by the Ccl21a gene, is primarily found in the thymus medulla and lymphoid tissues.
Purpose of the Study:
- To investigate the role of CCL21-Ser in antitumor immune responses.
- To analyze the impact of Ccl21a gene knockout on melanoma and other cancer types in mice.
Main Methods:
- Utilized Ccl21a-knockout (KO) mice to study tumor growth dynamics.
- Analyzed immune cell infiltration (CD8+ T cells, NK cells, Tregs) in tumors.
- Assessed co-inhibitory receptor expression (TIM-3, TIGIT) on Tregs.
Main Results:
- Ccl21a-KO mice exhibited significantly reduced growth of B16-F10 and YUMM1.7 melanomas.
- Tumors in Ccl21a-KO mice showed increased CD8+ T cell and NK cell infiltration and higher Treg counts.
- A reduced correlation between Treg/CD8+ T cell ratio and tumor weight was observed in Ccl21a-KO mice, with Tregs showing lower TIM-3 and TIGIT expression.
Conclusions:
- Endogenous CCL21-Ser supports melanoma growth in vivo.
- CCL21-Ser appears to maintain regulatory T cell function and suppress CD8+ T cell-mediated antitumor immunity.
