Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
J Neurooncol. 2020 Jan;146(1):139-146. doi: 10.1007/s11060-019-03355-0. Epub 2019 Nov 26.
The role of immune checkpoint molecules and the tumor immune microenvironment in the development of intracranial germ cell tumors remains unclear.
We investigated the expression of programed cell death-1 (PD-1), programed cell death ligand-1 (PD-L1), and tumor-infiltrating lymphocytes (TILs) in 8 patients who had intracranial germinomas with sufficient tumor tissue by immunohistochemistry, to analyze the associations between their clinical courses and radiological features. The 8 patients were categorized based on the duration between symptom onset and pathological diagnosis into the long-term onset (LTO) group (> 1 year of symptoms) and the short-term onset (STO) group (< 1 year of symptoms).
Three patients belonged to the LTO group and 5 patients to the STO group. Compared with STO tumors, LTO tumors were significantly associated with a lower ratio of PD-L1-positive tumor cells (p = 0.012), higher number of infiltrating CD3- and CD8-positive lymphocytes (p = 0.016, 0.003, respectively), and lower ratio of PD-1-positive cells per CD8-positive lymphocytes (p = 0.047). LTO germinomas were significantly smaller in size than STO tumors, not associated with hydrocephalus, and tended to be present in patients with older age at diagnosis and atypical tumor location.
Our data suggest that the tumor immune microenvironment, including PD-1/PD-L1 signaling, is associated with the growth of intracranial germinomas.
免疫检查点分子和肿瘤免疫微环境在颅内生殖细胞肿瘤发展中的作用尚不清楚。
我们通过免疫组织化学方法研究了 8 例颅内生殖细胞瘤患者的程序性细胞死亡蛋白-1(PD-1)、程序性细胞死亡配体-1(PD-L1)和肿瘤浸润淋巴细胞(TILs)的表达情况,分析了它们的临床过程和影像学特征之间的相关性。根据症状发作和病理诊断之间的时间长短,将 8 例患者分为长潜伏期(LTO)组(> 1 年症状)和短潜伏期(STO)组(< 1 年症状)。
3 例患者属于 LTO 组,5 例患者属于 STO 组。与 STO 肿瘤相比,LTO 肿瘤的 PD-L1 阳性肿瘤细胞比例明显较低(p=0.012),CD3 和 CD8 阳性浸润淋巴细胞数量明显较多(p=0.016,0.003),而 PD-1 阳性细胞与 CD8 阳性淋巴细胞的比例明显较低(p=0.047)。LTO 生殖细胞瘤的体积明显小于 STO 肿瘤,与脑积水无关,并且倾向于发生在诊断时年龄较大和肿瘤位置不典型的患者中。
我们的数据表明,肿瘤免疫微环境,包括 PD-1/PD-L1 信号通路,与颅内生殖细胞瘤的生长有关。