Laboratory of Experimental Immunology, IDI-IRCCS, 00167 Rome, Italy.
Laboratory of Molecular Oncology, IDI-IRCCS, 00167 Rome, Italy.
Int J Mol Sci. 2020 Apr 22;21(8):2950. doi: 10.3390/ijms21082950.
Therapy of multiple sclerosis (MS) with disease-modifying agents such as natalizumab or fingolimod has been associated with the development of cutaneous melanoma. Here we briefly revise literature data and report of a case of a 48-year old woman who developed a melanoma and several atypical naevi after sub sequential treatment with natalizumab (1 year) and fingolimod (7 years). By immunohistochemistry we observed the presence of T cells and leukocyte infiltration as well as of vascular endothelial growth factor (VEGF)-A expression in the patient melanoma biopsy. Then, we analyzed proliferation, migration and VEGF-A expression in three melanoma cell lines and found out that both natalizumab and fingolimod inhibited tumor cell proliferation but promoted or blocked cell migration depending on the cell line examined. VEGF-A secretion was augmented in one melanoma cell line only after fingolimod treatment. In conclusion, our in vitro data do not support the hypothesis of a direct action of natalizumab or fingolimod on melanoma progression but acting on the tumor microenvironment these treatments could indirectly favor melanoma evolution.
多发性硬化症（MS）的治疗方法，如那他珠单抗或芬戈莫德，可以与皮肤黑色素瘤的发展相关。在这里，我们简要地复习了文献数据，并报告了一例 48 岁女性的病例，她在接受那他珠单抗（1 年）和芬戈莫德（7 年）序贯治疗后，出现了黑色素瘤和几个非典型痣。通过免疫组织化学，我们观察到患者黑色素瘤活检中存在 T 细胞和白细胞浸润以及血管内皮生长因子（VEGF）-A 的表达。然后，我们分析了三种黑色素瘤细胞系的增殖、迁移和 VEGF-A 表达，发现那他珠单抗和芬戈莫德都抑制了肿瘤细胞的增殖，但根据所检查的细胞系，促进或阻断了细胞迁移。只有在用芬戈莫德治疗后，一种黑色素瘤细胞系的 VEGF-A 分泌才增加。总之，我们的体外数据不支持那他珠单抗或芬戈莫德直接作用于黑色素瘤进展的假说，但这些治疗方法作用于肿瘤微环境，可以间接地促进黑色素瘤的演变。
