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 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 -knockout (KO) mice. The 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 -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 -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 -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 by maintaining Treg function and suppressing antitumor immunity by CD8 T cells.