Manchester Centre for Clinical Neurosciences, Manchester, UK.
Geoffrey Jefferson Brain Research Centre, Manchester, UK.
Neurosurgery. 2023 Mar 1;92(3):581-589. doi: 10.1227/neu.0000000000002252. Epub 2022 Dec 12.
There is evidence that macrophage infiltration in the tumor microenvironment promotes vestibular schwannoma (VS) growth. Efficacy of bevacizumab in NF2-associated VS demonstrates the value of therapies targeting the microvascular tumor microenvironment, and tumor-associated macrophages (TAMs) may represent another druggable target.
To characterize the relationship between growth, TAM infiltration, and circulating monocyte chemokines in a large cohort of patients with VS.
Immunostaining for Iba1 (macrophages), CD31 (endothelium), and fibrinogen (permeability) was performed on 101 growing and 19 static sporadic VS. The concentrations of monocyte-specific chemokines were measured in the plasma of 50 patients with growing VS and 25 patients with static VS.
The Iba1 + cell count was significantly higher in growing as compared with static VS (592 vs 226/×20 HPF, P =<0.001). Similarly, the CD31 + % surface area was higher in growing VS (2.19% vs 1.32%, P = .01). There was a positive correlation between TAM infiltration and VS growth rate, which persisted after controlling for the effect of tumor volume (aR2 = 0.263, P =<0.001). The plasma concentrations of several monocytic chemokines were higher in patients with growing rather than static VS.
There is a strong positive correlation between TAM infiltration and volumetric growth of VS, and this relationship is independent of tumor size. There is a colinear relationship between TAM infiltration and tumor vascularity, implying that inflammation and angiogenesis are interlinked in VS. Chemokines known to induce monocyte chemotaxis are found in higher concentrations in patients with growing VS, suggestive of a potential pathophysiological mechanism.
有证据表明，肿瘤微环境中的巨噬细胞浸润促进听神经鞘瘤（VS）的生长。贝伐单抗在 NF2 相关 VS 中的疗效证明了靶向微血管肿瘤微环境的治疗方法的价值，而肿瘤相关巨噬细胞（TAMs）可能代表另一个可治疗的靶点。
在一个大型 VS 患者队列中，描述肿瘤生长、TAM 浸润与循环单核细胞趋化因子之间的关系。
对 101 例生长性 VS 和 19 例静止性 VS 进行 Iba1（巨噬细胞）、CD31（内皮）和纤维蛋白原（通透性）免疫染色。在 50 例生长性 VS 患者和 25 例静止性 VS 患者的血浆中测量单核细胞特异性趋化因子的浓度。
与静止性 VS 相比，生长性 VS 的 Iba1+细胞计数显著升高（592 对 226/×20 HPF，P<0.001）。同样，生长性 VS 的 CD31+%表面积也更高（2.19%对 1.32%，P=0.01）。TAM 浸润与 VS 生长速度呈正相关，且在控制肿瘤体积影响后仍然存在（aR2=0.263，P<0.001）。与静止性 VS 相比，生长性 VS 患者的几种单核细胞趋化因子的血浆浓度更高。
TAM 浸润与 VS 的体积生长之间存在很强的正相关，这种关系独立于肿瘤大小。TAM 浸润与肿瘤血管生成之间存在共线性关系，这表明炎症和血管生成在 VS 中相互关联。在生长性 VS 患者中发现已知可诱导单核细胞趋化的趋化因子浓度较高，提示存在潜在的病理生理机制。
