Quality Is King: Fundamental Insights into Tumor Antigenicity from Virus-Associated Merkel Cell Carcinoma

Lahman MC, Paulson KG, Nghiem PT, Chapuis AG

J Invest Dermatol. 2021 Apr 13;S0022-202X(21)00999-4. doi: 10.1016/j.jid.2020.12.037

PMID: 33863500

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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.

J Invest Dermatol. 2021 Apr 13;S0022-202X(21)00999-4. doi: 10.1016/j.jid.2020.12.037