Characterization of immunosuppressive myeloid cells in Merkel cell carcinoma: correlation with resistance to PD-1 pathway blockade

PD-(L)1 blockade has shown remarkable success in treating advanced Merkel cell carcinoma (MCC), but less than half patients experience durable benefit. Identifying the components of the tumor microenvironment that determine response to immunotherapy is crucial for developing future therapies. While CD8 T-cell infiltration is associated with better outcomes in MCC at initial diagnosis, intratumoral CD8 T cells are only partially predictive of response to PD-(L)1 blockade. Using single cell analytics, we identified tumor associated macrophages (TAMs) with an immunosuppressive phenotype. Infiltration of these TAMs was much more prevalent in tumors with abundant CD8 T cells. Indeed, upon linking to clinical response data, an elevated presence of TAMs was associated with a lower likelihood of response even in CD8-infiltrated tumors. These findings suggest that TAMs may actively suppress T cell function in MCC and that disrupting their activity could be a useful approach to improve the response to immunotherapy.