CD30 ligand deficiency accelerates glioma progression by promoting the formation of tumor immune microenvironment
CD30 ligand deficiency accelerates glioma progression by promoting the formation of tumor immune microenvironment
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CD30配体缺陷通过促进肿瘤免疫微环境的形成加速胶质瘤进展
DOI：
10.1016/j.intimp.2019.03.055
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发表时间：
2019-06-01
影响因子：
5.6
通讯作者：
Sun, Xun
中科院分区：
文献类型：
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作者：
Duan, Jin;Gao, Yaxian;Sun, Xun
CD30配体（CD30L、CD153）属于肿瘤坏死因子超家族，据报道主要在多种自身免疫性疾病和霍奇金淋巴瘤中发挥免疫调节作用。然而，人们对其在神经胶质瘤微环境中的调节知之甚少。在本研究中，使用GL261小鼠神经胶质瘤模型，我们发现宿主体内的CD30L缺乏会加速神经胶质瘤的生长并降低小鼠的存活率，这可能与肿瘤浸润免疫细胞的积累有关，特别是肿瘤相关巨噬细胞、骨髓源性抑制细胞和CD8(+) PD-1(+) T细胞。此外，与野生型小鼠相比，CD30L 缺陷导致肿瘤相关巨噬细胞的亚群不同。此外，与野生型小鼠相比，CD30L缺陷小鼠中的肿瘤相关巨噬细胞和小胶质细胞在肿瘤内呈现出更促肿瘤发生的表型。 CD30L 缺陷小鼠中的 CD8 + T 细胞降低了 ki-67 的表达。因此，这些结果表明CD30L缺陷促进CD8+T细胞的耗竭以及肿瘤相关巨噬细胞和小胶质细胞的浸润。我们的研究结果为针对 CD30/CD30L 信号传导的神经胶质瘤的新的潜在免疫疗法提供了证据。
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.