Section of Dermatology, Department of Surgical Sciences, Parma University, Via Gramsci 14, I-43100 Parma, Italy.
Eur J Dermatol. 2011 Mar-Apr;21(2):178-83. doi: 10.1684/ejd.2010.1240.
Melanoma progression is favoured by prevalence, within the micro-environment of primary cutaneous melanoma, of suppressive forces, e.g. exerted by CD4(+) CD25(+) FOXP3(+) regulatory T lymphocytes, over anti-melanoma immunity, e.g. exerted by CD8(+) cytolytic T lymphocytes. The CD27 glycoprotein is crucial because it is able to identify regulatory T cells endowed with strong suppressive ability, whilst CD8(+) T cells endowed with actual cytolytic ability become CD27(-). The present in situ quantitative immunohistochemical study, including a series of double labelling experiments and morphometrical cell analyses, shows that the vast majority of lymphocytes infiltrating primary cutaneous melanoma express CD27. Specifically, virtually the entire CD4(+) CD25(+) FOXP3(+) T subset infiltrating primary cutaneous melanoma also co-expressed CD27; CD27 was, moreover, co-expressed even by the vast majority of the CD8(+) T cells, and, conversely, effector/cytotoxic CD8(+)CD27(-) cells were very scarcely represented. The overwhelming CD27 co-expression may confer on the CD4(+)CD25(+)FOXP3(+) T subset a consistent capacity to suppress anti-melanoma immunity, whereas the too low CD8(+) CD27(-) cell proportion may presumably be insufficient to confer on the CD8(+) T subset a satisfactory anti-melanoma cytotoxic activity. We therefore propose that these CD27-discriminated pathways may trigger a functional imbalance within the microenvironment of primary cutaneous melanoma, thus favouring melanoma progression.
黑色素瘤的进展受到多种因素的影响,其中包括原发性皮肤黑色素瘤微环境中抑制性力量的优势,例如 CD4(+) CD25(+) FOXP3(+) 调节性 T 淋巴细胞的作用,以及抗黑色素瘤免疫的抑制,例如 CD8(+) 细胞毒性 T 淋巴细胞的作用。CD27 糖蛋白是至关重要的,因为它能够识别具有强大抑制能力的调节性 T 细胞,而具有实际细胞毒性能力的 CD8(+) T 细胞则成为 CD27(-)。本原位定量免疫组织化学研究包括一系列双标记实验和形态计量学细胞分析,显示绝大多数浸润原发性皮肤黑色素瘤的淋巴细胞表达 CD27。具体而言,浸润原发性皮肤黑色素瘤的几乎所有 CD4(+) CD25(+) FOXP3(+) T 细胞亚群也共同表达 CD27;此外,CD27 甚至还表达于绝大多数 CD8(+) T 细胞上,而效应/细胞毒性 CD8(+) CD27(-) 细胞则非常罕见。压倒性的 CD27 共表达可能赋予 CD4(+) CD25(+) FOXP3(+) T 细胞亚群持续抑制抗黑色素瘤免疫的能力,而 CD8(+) CD27(-) 细胞比例过低可能不足以赋予 CD8(+) T 细胞亚群令人满意的抗黑色素瘤细胞毒性活性。因此,我们提出这些 CD27 区分的途径可能在原发性皮肤黑色素瘤的微环境中引发功能失衡,从而促进黑色素瘤的进展。