T-Cell Repertoire in Combination with T-Cell Density Predicts Clinical Outcomes in Patients with Merkel Cell Carcinoma

• Published in: Journal of investigative dermatology Vol. 140; no. 11; pp. 2146 - 2156.e4
• Main Authors: Farah, Maya, Reuben, Alexandre, Spassova, Ivelina, Yang, Richard K., Kubat, Linda, Nagarajan, Priyadharsini, Ning, Jing, Li, Wen, Aung, Phyu P., Curry, Jonathan L., Torres-Cabala, Carlos A., Hudgens, Courtney W., Ugurel, Selma, Schadendorf, Dirk, Gumbs, Curtis, Little, Latasha D., Futreal, Andrew, Wistuba, Ignacio I., Prieto, Victor G., Wang, Linghua, Wong, Michael K., Wargo, Jennifer A., Becker, Jürgen C., Tetzlaff, Michael T.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2020
• Subjects: Adult; Aged; Aged, 80 and over; Carcinoma, Merkel Cell - immunology; Carcinoma, Merkel Cell - mortality; Carcinoma, Merkel Cell - pathology; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prognosis; Receptors, Antigen, T-Cell - immunology; Skin Neoplasms - immunology; Skin Neoplasms - mortality; Skin Neoplasms - pathology; T-Lymphocytes - immunology; LN; TCR; OS; DSS; MDACC; UDE; SDom; MCPyV; MCC; MCPyV(−); MCPyV(+)
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1016/j.jid.2020.02.031

The integrity of the immune system represents a pivotal risk factor and prognostic biomarker for Merkel cell carcinoma. A higher density of tumor-associated T cells correlates with improved Merkel cell carcinoma–specific survival, but the prognostic importance of the T-cell infiltrate reactivity is unknown. We evaluated the T-cell receptor repertoire associated with 72 primary Merkel cell carcinomas and correlated metrics of the T-cell receptor repertoire with clinicopathologic characteristics and patient outcomes. We showed that a high Simpson’s Dominance index (SDom) was significantly associated with fewer metastases (P = 0.01), lower stage at presentation (P = 0.02), lower final stage at last follow-up (P = 0.05), and longer time to first lymph node metastasis (P = 0.04). These correlations were mostly preserved in the Merkel cell polyomavirus–negative subgroup. Combining SDom with CD3+ or CD8+ T-cell density revealed three distinct prognostic groups with respect to disease-specific survival. Patients with both high SDom and high CD3+ or CD8+ T-cell density had markedly improved disease-specific survival compared with patients with low SDom and low CD3+ or CD8+ T-cell density (P = 0.002 and P = 0.03, respectively). Patients with either high SDom or high CD3+ or CD8+ had intermediate disease-specific survival. Our findings demonstrate that the quality of the tumor-associated T-cell infiltrate informs patient prognosis in primary Merkel cell carcinoma beyond the T-cell density.