A comparison of myeloid-derived suppressor cell populations in patients with ulcerated vs non-ulcerated melanoma receiving immune checkpoint blockade

Abstract

Myeloid-derived suppressor cells (MDSCs) are expanded in cancer patients, have an intrinsic immunosuppressive function, and thus may play a role in resistance to immunotherapy. Ulceration of the melanoma primary is associated with more aggressive disease and is an independent prognostic factor for melanoma-specific survival. However, the underlying factors contributing to this more aggressive phenotype are not completely understood. The current study aims to correlate changes in circulating MDSC during immunotherapy in patients with ulcerated vs non-ulcerated melanoma primary tumors. Longitudinal changes in levels of circulating MDSCs were analyzed via flow cytometry in melanoma patients receiving immune checkpoint inhibitors (ICIs) and stratified by ulceration status. Following the initiation of therapy, the percentage of total MDSCs increased significantly in patients with both ulcerated ( P = 0.003) and non-ulcerated ( P < 0.001) tumors. When MDSCs were stratified by subset, the proportion of granulocytic MDSC (PMN-MDSC) decreased in patients with non-ulcerated tumors ( P = 0.023), while the proportion remained stable in patients with ulcerated tumors ( P = 0.121). The reduction in the proportion PMN-MDSC in non-ulcerated patients coincided with a statistically significant increase in the proportion of CD14 + /CD15 + MDSC ( P = 0.008), resulting in a greater proportion of CD14 + /CD15 + MDSC in non-ulcerated patients as compared to ulcerated melanoma patients following two infusions of ICIs (27.3 ± 19.2% vs 16.1 ± 19.2%; P = 0.008). The trajectories of the MDSC populations described here provide insight into the altered tumor microenvironment in ulcerated melanoma and highlight key changes in a cell population that could contribute to immunotherapy resistance.