Jennewein Lukas, Bartsch Georg, Gust Kilian, Kvasnicka Hans-Michael, Haferkamp Axel, Blaheta Roman, Mittelbronn Michel, Harter Patrick N, Mani Jens
Neurological Institute (Edinger Institute), Goethe University, D-60528 Frankfurt/Main, Germany.
Department of Obstetrics and Gynecology, Goethe University, D-60590 Frankfurt/Main, Germany.
Oncol Lett. 2018 Jun;15(6):9852-9860. doi: 10.3892/ol.2018.8597. Epub 2018 Apr 27.
Testicular germ cell cancer in a metastatic state is curable with a cisplatin-based first line chemotherapy. However, 10-15% of these patients are resistant to first line chemotherapy and are thus left with only palliative options. Immunotherapies and inhibition of angiogenesis used in multiple types of cancer; however, the molecular context of angiogenesis and immune checkpoints in the development and progression of testicular cancers is still unknown. Therefore, the present study performed tissue micro array based analysis of 84 patients with immunohistochemistry of programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1) and vascular endothelial growth factor receptor 2 (VEGFR2) of testicular cancer and corresponding normal appearing testis tissue, matching the results with clinical data. The results demonstrated that PD-L1 was significantly upregulated in testicular tumors and that PD-1 positive cells significantly infiltrated the testicular tumor when compared with normal testicular tissue. VEGFR2 was significantly upregulated in testicular cancer. It was indicated that PD-1 expressing cytotoxic cells may require pathologic tumor vessels to pass the blood-testis-barrier in order to migrate into the tumor. Notably, when matching the clinical data for PD-1, PD-L1 and VEGFR2 there were no differences in expression in the different International Germ Cell Cancer Collaborative Group stages of non-seminoma. These data suggested that the anti-PD-1/PD-L1 immunotherapy and the anti-angiogenic therapy, sequentially or in combination, may be a promising option in the treatment of testicular cancer.
处于转移状态的睾丸生殖细胞癌可通过以顺铂为基础的一线化疗治愈。然而，这些患者中有10 - 15%对一线化疗耐药，因此只剩下姑息治疗方案。免疫疗法和血管生成抑制已用于多种癌症；然而，血管生成和免疫检查点在睾丸癌发生和发展中的分子背景仍不清楚。因此，本研究对84例睾丸癌患者及相应的外观正常的睾丸组织进行了基于组织微阵列的分析，采用免疫组织化学检测程序性细胞死亡蛋白1（PD - 1）、程序性细胞死亡配体1（PD - L1）和血管内皮生长因子受体2（VEGFR2），并将结果与临床数据进行匹配。结果表明，与正常睾丸组织相比，PD - L1在睾丸肿瘤中显著上调，且PD - 1阳性细胞显著浸润睾丸肿瘤。VEGFR2在睾丸癌中显著上调。这表明表达PD - 1的细胞毒性细胞可能需要病理性肿瘤血管穿过血睾屏障才能迁移到肿瘤中。值得注意的是，当将PD - 1、PD - L1和VEGFR2的临床数据进行匹配时，在非精原细胞瘤的不同国际生殖细胞癌协作组分期中，其表达没有差异。这些数据表明，抗PD - 1/PD - L1免疫疗法和抗血管生成疗法，序贯或联合使用，可能是治疗睾丸癌的一个有前景的选择。
