Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium.
Lab of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
Elife. 2020 Feb 4;9:e52176. doi: 10.7554/eLife.52176.
Cancer immunotherapy by immune checkpoint blockade has proven its great potential by saving the lives of a proportion of late stage patients with immunogenic tumor types. However, even in these sensitive tumor types, the majority of patients do not sufficiently respond to the therapy. Furthermore, other tumor types, including glioblastoma, remain largely refractory. The glioblastoma immune microenvironment is recognized as highly immunosuppressive, posing a major hurdle for inducing immune-mediated destruction of cancer cells. Scattered information is available about the presence and activity of immunosuppressive or immunostimulatory cell types in glioblastoma tumors, including tumor-associated macrophages, tumor-infiltrating dendritic cells and regulatory T cells. These cell types are heterogeneous at the level of ontogeny, spatial distribution and functionality within the tumor immune compartment, providing insight in the complex cellular and molecular interplay that determines the immune refractory state in glioblastoma. This knowledge may also yield next generation molecular targets for therapeutic intervention.
免疫检查点阻断的癌症免疫疗法通过挽救一部分具有免疫原性肿瘤类型的晚期患者的生命，已经证明了其巨大的潜力。然而，即使在这些敏感的肿瘤类型中，大多数患者对治疗的反应也不够充分。此外，包括胶质母细胞瘤在内的其他肿瘤类型仍然很大程度上难以治疗。胶质母细胞瘤的免疫微环境被认为具有高度免疫抑制性，这对诱导免疫介导的癌细胞破坏构成了重大障碍。关于胶质母细胞瘤肿瘤中存在和活性的免疫抑制性或免疫刺激性细胞类型的信息较为分散，包括肿瘤相关巨噬细胞、肿瘤浸润树突状细胞和调节性 T 细胞。这些细胞类型在肿瘤免疫区室中的个体发生、空间分布和功能水平上具有异质性，为决定胶质母细胞瘤免疫抵抗状态的复杂细胞和分子相互作用提供了深入了解。这些知识也可能为治疗干预提供下一代分子靶点。
