CD30 ligand deficiency accelerates glioma progression by promoting the formation of tumor immune microenvironment.

CD30 ligand (CD30L, CD153), belonging to the tumor necrosis factor superfamily, has been reported to act as an immune regulator mainly in several autoimmune diseases and Hodgkin's lymphoma. However, little is known about its regulation in the glioma microenvironment. In this study, using a GL261 mouse glioma model, we showed that CD30L deficiency in the host accelerated glioma growth and reduced mouse survival, which might be associated with the accumulation of tumor-infiltrating immune cells, especially tumor-associated macrophages, myeloid-derived suppressor cells and CD8 ⁺ PD-1 ⁺ T cells. Moreover, CD30L deficiency resulted in distinct subsets of tumor-associated macrophages compared with those of wild-type mice. Furthermore, compared with those of wild-type mice, tumor-associated macrophages and microglia in CD30L-deficient mice adopted a more pro-tumorigenic phenotype within tumors. CD8 ⁺ T cells in CD30L-deficient mice decreased the expression of ki-67. Therefore, these results suggest that CD30L deficiency promotes the exhaustion of CD8 ⁺ T cells and the infiltration of tumor-associated macrophages and microglia. Our findings provide evidence for a new potential immunotherapy for glioma targeting CD30/CD30L signaling.
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