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Merkel cell carcinomas infiltrated with CD33(+) myeloid cells and CD8(+) T cells are associated with improved outcome
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International audience. BACKGROUND: Merkel cell carcinoma (MCC) is a rare tumor of the skin with an aggressive behavior. Immunity is the main regulator of MCC development, and many interactions between lymphocytes and tumor cells have been proven. However, the impact of tumor-infiltrating myeloid cells (TIMs) needs better characterization. OBJECTIVE: To characterize TIMs in MCC and their association with other immune effectors and patient outcome. METHODS: MCC cases were reviewed from a historical/prospective cohort. In all, 103 triplicate tumor samples were included in a tissue microarray. Macrophages, neutrophils and myeloid-derived suppressor cells were characterized by the following markers: CD68, CD33, CD163, CD15, and CD33(+)/HLA-DR(-). The association between these populations and PD-L1 expression, CD8 infiltrates and vascular density was assessed. Impact on survival was analyzed by log-rank tests and a Cox multivariate model. RESULTS: The median density of macrophages was 216/mm(2). CD68(+) and CD33(+) macrophage densities were associated with CD8 infiltrates and PD-L1 expression. In addition, MCC harboring infiltration of CD8 T cells and brisk CD33 myeloid-cell infiltrates was significantly and independently associated with improved outcome (MCC recurrence and death). LIMITATIONS: Sampling bias and retrospective design. CONCLUSION: Infiltration of CD33 myeloid cells and CD8 lymphocytes defines a subset of MCC associated with improved outcome.
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