Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50937 Cologne, Germany.
Int J Mol Sci. 2022 Jan 27;23(3):1478. doi: 10.3390/ijms23031478.
Conjunctival melanoma (CM) accounts for 5% of all ocular melanomas and arises from malignantly transformed melanocytes in the conjunctival epithelium. Current therapies using surgical excision in combination with chemo- or cryotherapy still have high rates for recurrences and metastatic disease. Lately, novel signal transduction-targeted and immune checkpoint inhibitors like cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, programmed cell death protein-1 (PD-1) receptor inhibitors, BRAF- or MEK-inhibitors for systemic treatment of melanoma have improved the outcome even for unresectable cutaneous melanoma, improving patient survival dramatically. The use of these therapies is now also recommended for CM; however, the immunological background of CM is barely known, underlining the need for research to better understand the immunological basics when treating CM patients with immunomodulatory therapies. Immune checkpoint inhibitors activate tumor defense by interrupting inhibitory interactions between tumor cells and T lymphocytes at the so-called checkpoints. The tumor cells exploit these inhibitory targets on T-cells that are usually used by dendritic cells (DCs). DCs are antigen-presenting cells at the forefront of immune response induction. They contribute to immune tolerance and immune defense but in the case of tumor development, immune tolerance is often prevalent. Enhancing the immune response via DCs, interfering with the lymphatic pathways during immune cell migration and tumor development and specifically targeting tumor cells is a major therapeutic opportunity for many tumor entities including CM. This review summarizes the current knowledge on the function of lymphatic vessels in tumor growth and immune cell transport and continues to compare DC subsets in CM with related melanomas, such as cutaneous melanoma and mucosal melanoma.
结膜黑色素瘤 (CM) 占所有眼部黑色素瘤的 5%，起源于结膜上皮中恶性转化的黑色素细胞。目前采用手术切除联合化疗或冷冻治疗的方法，仍有很高的复发和转移疾病的风险。最近，新型信号转导靶向和免疫检查点抑制剂，如细胞毒性 T 淋巴细胞相关蛋白 4 (CTLA-4) 抑制剂、程序性细胞死亡蛋白-1 (PD-1) 受体抑制剂、BRAF 或 MEK 抑制剂，用于黑色素瘤的全身治疗，甚至提高了不可切除的皮肤黑色素瘤的疗效，显著改善了患者的生存。目前也推荐将这些疗法用于 CM；然而，CM 的免疫学背景几乎未知，这凸显了研究的必要性，以便在使用免疫调节疗法治疗 CM 患者时更好地了解免疫学基础。免疫检查点抑制剂通过阻断肿瘤细胞和 T 淋巴细胞之间在所谓的检查点的抑制性相互作用来激活肿瘤防御。肿瘤细胞利用 T 细胞上的这些抑制性靶点，而这些靶点通常被树突状细胞 (DCs) 使用。DCs 是免疫反应诱导前沿的抗原呈递细胞。它们有助于免疫耐受和免疫防御，但在肿瘤发展的情况下，免疫耐受通常更为常见。通过 DC 增强免疫反应，干扰免疫细胞迁移和肿瘤发展过程中的淋巴途径，特异性靶向肿瘤细胞，这是包括 CM 在内的许多肿瘤实体的主要治疗机会。本文综述了淋巴管在肿瘤生长和免疫细胞运输中的作用的最新知识，并继续将 CM 中的 DC 亚群与相关黑色素瘤（如皮肤黑色素瘤和黏膜黑色素瘤）进行比较。
