Merkel cell carcinomas infiltrated with CD33+ myeloid cells and CD8+ T cells are associated with improved outcome

Abstract

Background: Merkel cell carcinoma (MCC) is a rare tumor of the skin that has 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 needs better characterization.

Objective: To characterize tumor-infiltrating myeloid cells in MCC and their association with other immune effectors and patient outcome.

Methods: MCC cases were reviewed from an ongoing prospective cohort study. 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, CD33, and human leukocyte antigen-DR. Associations of these cell populations with programmed cell death ligand 1 expression, CD8 infiltrates, and vascular density were assessed. Impact on survival was analyzed by log-rank tests and a Cox multivariate model.

Results: The median density of macrophages was 216 cells/mm². CD68⁺ and CD33⁺ macrophage densities were associated with CD8⁺ T-cell infiltrates and programmed cell death ligand 1 expression. In addition, MCC harboring CD8⁺ T cell infiltrates and brisk CD33⁺ myeloid cell infiltrates were significantly and independently associated with improved outcomes (recurrence-free and overall survival).

Limitations: Sampling bias and the retrospective design were potential study limitations.

Conclusion: Infiltration of CD33⁺ myeloid cells and CD8⁺ T lymphocytes defines a subset of MCC associated with improved outcome.

Keywords: CD33; Merkel cell carcinoma; PD-L1; immune infiltrate; macrophages; myeloid cells.