Center for Skull Base and Pituitary Surgery, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School.
Department of Pathology, Boston Children's Hospital, Boston, Massachusetts.
Otol Neurotol. 2020 Dec;41(10):e1290-e1296. doi: 10.1097/MAO.0000000000002782.
Vestibular schwannomas exhibit a uniquely variable natural history of growth, stability, or even spontaneous regression. We hypothesized that a transitory population of immune cells, or immunomodulation of tumors cells, may influence the growth pattern of schwannomas. We therefore sought to characterize the impact of the immune microenvironment on schwannoma behavior.
Forty-eight vestibular schwannomas with preoperative magnetic resonance imaging and 11 with serial imaging were evaluated for presence of immune infiltrates (including the pan-leukocyte marker Cluster of Differentiation (CD)45, CD4 and CD8 T-cell, and CD68 and CD163 macrophages) as well as expression of immunomodulatory regulators (Programmed Death Ligand 1 (PD-L1), Programmed Death Ligand 2 (PD-L2), LAG-3, TIM-3, V-domain Ig Suppressor of T cell Activation). Maximal diameter, volume, and recurrence were annotated.
Vestibular schwannomas were characterized by diverse signatures of tumor infiltrating leukocytes and immunomodulatory markers. The median tumor volume was 4.7 cm (Interquartile Range (IQR) 1.0-13.0) and maximum diameter was 2.3 cm (IQR 1.5-3.2). Among tumors with serial imaging, the median volumetric growth was 0.04 cm/mo (IQR 0.01-0.18). Tumor volume and maximum diameter demonstrated strong concordance (R = 0.90; p < 0.001). Vestibular schwannoma volume was positively associated with CD4, CD68, and CD163, but not CD8, immune infiltration (all p < 0.05). Tumor growth was positively associated with CD163 and PD-L1 (both p < 0.05). Further, CD163 modified this effect: the relationship between PD-L1 and growth strengthened with increasing CD163 infiltration (R = 0.81, p = 0.007). No other immune cell types modified this relationship. These associations were inconsistently observed for maximum diameter and linear growth.
Vestibular schwannomas demonstrate variable expression of immune regulatory markers as well as immune infiltrates. Tumor size is associated with immune infiltrates and tumor growth is associated with PD-L1, especially in the presence of M2-subtype macrophages. Volumetric measures may associate with the biological signature more accurately than linear parameters. Future exploration of the role of immune modulation in select schwannomas will further enhance our understanding of the biology of these tumors and suggest potential therapeutic avenues for control of tumor growth.
前庭神经鞘瘤的生长、稳定甚至自发消退具有独特的多变的自然史。我们假设，一过性免疫细胞群或肿瘤细胞的免疫调节可能会影响神经鞘瘤的生长模式。因此，我们试图描述免疫微环境对神经鞘瘤行为的影响。
对 48 例术前磁共振成像（MRI）和 11 例有连续影像学检查的前庭神经鞘瘤进行评估，以检测免疫浸润情况（包括白细胞标志物簇分化（CD）45、CD4 和 CD8 T 细胞以及 CD68 和 CD163 巨噬细胞）以及免疫调节调节剂的表达（程序性死亡配体 1（PD-L1）、程序性死亡配体 2（PD-L2）、LAG-3、TIM-3、V 结构域 Ig 抑制 T 细胞激活）。标注最大直径、体积和复发情况。
前庭神经鞘瘤的特征是浸润白细胞和免疫调节标志物的不同特征。肿瘤体积中位数为 4.7cm（四分位距（IQR）1.0-13.0），最大直径中位数为 2.3cm（IQR 1.5-3.2）。在有连续影像学检查的肿瘤中，体积平均增长率为 0.04cm/月（IQR 0.01-0.18）。肿瘤体积和最大直径之间具有很强的一致性（R=0.90；p<0.001）。神经鞘瘤体积与 CD4、CD68 和 CD163 呈正相关，但与 CD8 免疫浸润无关（均 p<0.05）。肿瘤生长与 CD163 和 PD-L1 呈正相关（均 p<0.05）。此外，CD163 改变了这种关系：PD-L1 与生长之间的关系随着 CD163 浸润的增加而增强（R=0.81，p=0.007）。其他免疫细胞类型没有改变这种关系。这些关联在最大直径和线性生长方面不一致。
前庭神经鞘瘤表现出免疫调节标志物以及免疫浸润的不同表达。肿瘤大小与免疫浸润有关，肿瘤生长与 PD-L1 有关，尤其是在存在 M2 型巨噬细胞时。体积测量可能比线性参数更准确地与生物学特征相关。进一步探索免疫调节在特定神经鞘瘤中的作用将有助于我们更好地了解这些肿瘤的生物学特性，并为控制肿瘤生长提供潜在的治疗途径。
