Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA; Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA; Medical Oncology, Swedish Cancer Institute, Seattle, Washington, USA; Elson S. Floyd College of Medicine, Washington State University, Spokane, Washington, USA.
J Invest Dermatol. 2021 Aug;141(8):1897-1905. doi: 10.1016/j.jid.2020.12.037. Epub 2021 Apr 13.
Merkel cell carcinoma (MCC) is a rare skin malignancy that is a paradigm cancer for solid tumor immunotherapy. MCCs associated with Merkel cell polyomavirus (virus-positive MCC [VP-MCC]) or chronic UV exposure (virus-negative MCC [VN-MCC]) are anti-PD(L)1 responsive, despite VP-MCC's low mutational burden. This suggests that antigen quality, not merely mutation quantity, dictates immunotherapy responsiveness, and cell-based therapies targeting optimal antigens may be effective. Despite VP-MCC's antigenic homogeneity, diverse T-cell infiltration patterns are observed, implying microenvironment plasticity and multifactorial contributions to immune recognition. Moreover, VP-MCC exemplifies how antitumor adaptive immunity can provide tumor burden biomarkers for early detection and disease monitoring.
Merkel 细胞癌（MCC）是一种罕见的皮肤恶性肿瘤，是实体瘤免疫治疗的典范。与 Merkel 细胞多瘤病毒（病毒阳性 MCC [VP-MCC]）或慢性 UV 暴露相关的 MCC（病毒阴性 MCC [VN-MCC]）对 PD(L)1 有反应，尽管 VP-MCC 的突变负担较低。这表明抗原质量而不仅仅是突变数量决定了免疫治疗的反应性，并且针对最佳抗原的细胞疗法可能是有效的。尽管 VP-MCC 的抗原同质性，但观察到不同的 T 细胞浸润模式，这意味着微环境的可塑性和多种因素对免疫识别的贡献。此外，VP-MCC 为例说明了抗肿瘤适应性免疫如何为早期检测和疾病监测提供肿瘤负担生物标志物。
