Our team based in Seattle conducted a comprehensive review including evolving trends in the management of Merkel cell carcinoma (MCC). This summary covers key decision points, including recommended work-up during initial diagnosis, treatment options for MCC when it’s in one place or has spread, management of recurrent MCC, and new treatments that are showing promise with fewer side effects and good results. This review gives valuable information on how to handle MCC overall and emphasizes new methods that are effective and less toxic on patients.
Merkel Cell carcinoma (MCC) is a rare, aggressive human skin cancer with poor prognosis for advanced disease (Harms et al. 2016). The oncovirus Merkel cell polyomavirus (MCPyV) is associated with at least 80% of MCC cases (Feng et al. 2008) with persistent expression of the viral T antigens (T-Ag; large T antigen (LTA) and small T antigen (STA)) driving oncogenesis (Shuda et al. 2008). Immune surveillance is critical for tumor control. Highlighted by associations between survival and intratumoral levels of CD3+ and CD8+ lymphocytes (Paulson et al. 2014; Sihto and Joensuu 2012), and T-Ag-specific T-cells (Miller et al. 2017). As well as the high efficacy of checkpoint inhibitors (D’Angelo et al. 2018; Nghiem et al. 2016; Topalian et al. 2020). Nevertheless, for half of the patients, this treatment strategy is insufficient. Instead, T-cell-based therapies, such as cell therapies or vaccines, could be attractive, but require identification of CD8+ T-cell epitopes within T-Ag that serve as targets for tumor cell elimination. Several T-Ag-derived epitopes have been identified for a limited number of HLA haplotypes (Iyer et al. 2011; Jing et al. 2020; Lyngaa et al. 2014; Samimi et al. 2019), which reduces such applications to patients with the given HLA haplotypes. In addition, limited evidence is available for natural processing and MHC class I presentation of T-Ag-derived epitopes on MCC tumors, which is essential for T-cell-mediated tumor cell elimination. We, therefore, aimed to expand the repertoire of T-Ag-derived epitopes by creating a library of 146 potential CD8+ T-cell epitopes derived from STA, truncated LTA, including their shared common T antigen (CT) region, and viral capsid protein 1 (VP1) (Figure S1a, and Table S1). The majority of peptides were restricted to the newly evaluated HLA haplotypes, HLA-A*24:02, -B*08:01, -B*35:01, and -B*44:02 (Figure 1a), selected through in-silico predictions of HLA binding. T-cell epitopes restricted to HLA-A*01:01, -A*02:01, -A*03:01, -A*11:01, and -B*07:02 were previously described by Lyngaa et al. Additional HLA-matched control epitopes from common non-oncogenic viruses were included as positive controls for the T-cell detection process.