Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Nuffield Building, Crown Street, Liverpool, L69 3BX, UK.
Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK.
Cancer Immunol Immunother. 2023 Oct;72(10):3387-3393. doi: 10.1007/s00262-023-03499-z. Epub 2023 Jul 21.
Brain metastases are the most common intracranial tumors with an increasing incidence. They are an important cause of morbidity and mortality in patients with solid organ cancer and a focus of recent clinical research and experimental interest. Immune checkpoint inhibitors are being increasingly used to treat solid organ cancers.
To determine whether immune checkpoint inhibitors were biologically effective in the brain, we compared melanoma brain metastasis samples where treatment with ipilimumab had occurred preoperatively to those who had not received any immune modulating therapy and looked for histopathological (invasion, vascularity, metastasis inducing proteins, matrix metalloproteinases, immune cell infiltration, tissue architecture) and advanced MRI differences (diffusion weighted imaging).
Co-localized tissue samples from the same regions as MRI regions of interest showed significantly lower vascularity (density of CD34 + vessels) in the core and higher T-cell infiltration (CD3 + cells) in the leading edge for ipilimumab-treated brain metastasis samples than for untreated cases and this correlated with a higher tumor ADC signal at post-treatment/preoperative MRI brain.
Treatment of a melanoma brain metastasis with ipilimumab appears to cause measurable biological changes in the tumor that can be correlated with post-treatment diffusion weighted MRI imaging, suggesting both a mechanism of action and a possible surrogate marker of efficacy.
脑转移瘤是最常见的颅内肿瘤，发病率呈上升趋势。它们是实体瘤患者发病率和死亡率的重要原因，也是最近临床研究和实验关注的焦点。免疫检查点抑制剂越来越多地被用于治疗实体瘤。
为了确定免疫检查点抑制剂在大脑中是否具有生物学效应，我们比较了术前接受伊匹单抗治疗的黑色素瘤脑转移瘤样本和未接受任何免疫调节治疗的样本，并寻找组织病理学（浸润、血管生成、转移诱导蛋白、基质金属蛋白酶、免疫细胞浸润、组织结构）和高级 MRI 差异（扩散加权成像）。
与 MRI 感兴趣区相同区域的共定位组织样本显示，与未治疗的病例相比，伊匹单抗治疗的脑转移瘤样本的核心区域血管密度（CD34+血管密度）显著降低，前沿区域的 T 细胞浸润（CD3+细胞）增加，这与治疗后/术前 MRI 脑肿瘤的 ADC 信号升高相关。
用伊匹单抗治疗黑色素瘤脑转移瘤似乎会导致肿瘤发生可测量的生物学变化，这些变化可以与治疗后的扩散加权 MRI 成像相关，提示作用机制和可能的疗效替代标志物。
