Department of Biomedical and Neuromotor Sciences, Section of Anatomic Pathology "M. Malpighi", Bellaria Hospital, 40139, Bologna, Italy.
Department of Pathology, Rizzoli Institute, 40136, Bologna, Italy.
Endocr Pathol. 2020 Mar;31(1):21-32. doi: 10.1007/s12022-019-09601-5.
Merkel cell carcinoma is a rare (∼ 2000 cases/year in the USA) but aggressive neuroendocrine neoplasm of the skin. In 2008, the Merkel cell polyomavirus (MCPyV) was found to be clonally integrated in approximately 80% of Merkel cell carcinomas. The remaining 20% have large numbers of UV-associated mutations. Importantly, both the UV-induced neoantigens in virus-negative Merkel cell carcinoma and the Merkel cell polyomavirus oncogenes that are required for virus-positive tumor growth are highly immunogenic. Indeed, antigen-specific T cells detected in patients are frequently "dysfunctional/exhausted," and the inhibitory ligand PD-L1 is often expressed by Merkel cell carcinoma cells. These data led to point our attention on the quantity and the quality of the immune response in Merkel cell carcinoma. Here, we found CD8+ lymphocytes are the only singly evaluated lymphocyte subclass that strongly influenced overall survival and disease-specific survival in Merkel cell carcinoma. In addition, we highlighted as Merkel cell polyomavirus is a strong prognostic factor and as it prompts a host immune response involving various lymphocyte subclasses (CD3, CD8, FoxP3, and PD-L1 positive) in MCC. For this reason, we proposed a novel eye-based "immunoscore" model, obtained by tumor infiltrating lymphocytes subtyping (CD3, CD8, FoxP3, and PD-L1) that could provide additional prognostic information in Merkel cell carcinoma.
默克尔细胞癌是一种罕见的皮肤神经内分泌肿瘤（美国每年约有 2000 例），但具有侵袭性。2008 年，发现默克尔细胞多瘤病毒（MCPyV）在大约 80%的默克尔细胞癌中呈克隆整合。其余 20%的肿瘤有大量与紫外线相关的突变。重要的是，病毒阴性的默克尔细胞癌中的紫外线诱导的新抗原和病毒阳性肿瘤生长所需的默克尔细胞多瘤病毒致癌基因都具有高度免疫原性。事实上，在患者中检测到的抗原特异性 T 细胞经常是“功能失调/耗竭”的，而 PD-L1 抑制配体经常由默克尔细胞癌表达。这些数据使我们注意到默克尔细胞癌中免疫反应的数量和质量。在这里，我们发现 CD8+淋巴细胞是唯一被单独评估的淋巴细胞亚群，强烈影响默克尔细胞癌的总生存率和疾病特异性生存率。此外，我们强调默克尔细胞多瘤病毒是一个强有力的预后因素，因为它会引发涉及各种淋巴细胞亚群（CD3、CD8、FoxP3 和 PD-L1 阳性）的宿主免疫反应。出于这个原因，我们提出了一种新的基于眼睛的“免疫评分”模型，该模型通过肿瘤浸润淋巴细胞亚群（CD3、CD8、FoxP3 和 PD-L1）进行分类，可以为默克尔细胞癌提供额外的预后信息。
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