Haberthur Kristen, Brennan Kathryn, Hoglund Virginia, Balcaitis Stephanie, Chinn Harrison, Davis Amira, Kreuser Shannon, Winter Conrad, Leary Sarah E S, Deutsch Gail H, Ellenbogen Richard G, Crane Courtney A
a Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute , Seattle , WA , USA.
b University of Michigan , Department of Immunology , Ann Arbor , MI , USA.
Cancer Biol Ther. 2016 Dec;17(12):1253-1265. doi: 10.1080/15384047.2016.1250047. Epub 2016 Nov 11.
Adult brain tumors establish an immunosuppressive tumor microenvironment as a modality of immune escape, with several immunotherapies designed to overcome this barrier. However, the relationship between tumor cells and immune cells in pediatric brain tumor patients is not as well-defined. In this study, we sought to determine whether the model of immune escape observed in adult brain tumors is reflected in patients with pediatric brain tumors by evaluating NKG2D ligand expression on tissue microarrays created from patients with a variety of childhood brain tumor diagnoses, and infiltration of Natural Killer and myeloid cells. We noted a disparity between mRNA and protein expression for the 8 known NKG2D ligands. Surprisingly, high-grade gliomas did not have increased NKG2D ligand expression compared to normal adjacent brain tissue, nor did they have significant myeloid or NK cell infiltration. These data suggest that pediatric brain tumors have reduced NK cell-mediated immune surveillance, and a less immunosuppressive tumor microenvironment as compared to their adult counterparts. These data indicate that therapies aimed to improve NK cell trafficking and functions in pediatric brain tumors may have a greater impact on anti-tumor immune responses and patient survival, with fewer obstacles to overcome.
成人脑肿瘤会建立一种免疫抑制性肿瘤微环境作为免疫逃逸的一种方式,有几种免疫疗法旨在克服这一障碍。然而,小儿脑肿瘤患者中肿瘤细胞与免疫细胞之间的关系尚不明确。在本研究中,我们试图通过评估从患有各种儿童脑肿瘤诊断的患者创建的组织微阵列上NKG2D配体的表达以及自然杀伤细胞和髓样细胞的浸润情况,来确定在成人脑肿瘤中观察到的免疫逃逸模式是否在小儿脑肿瘤患者中有所体现。我们注意到8种已知NKG2D配体的mRNA和蛋白质表达之间存在差异。令人惊讶的是,与相邻正常脑组织相比,高级别胶质瘤的NKG2D配体表达并未增加,它们也没有显著的髓样细胞或NK细胞浸润。这些数据表明,与成人脑肿瘤相比,小儿脑肿瘤的NK细胞介导的免疫监视功能降低,肿瘤微环境的免疫抑制作用较小。这些数据表明,旨在改善小儿脑肿瘤中NK细胞运输和功能的疗法可能对抗肿瘤免疫反应和患者生存产生更大影响,且需要克服的障碍较少。