A Population of HLA-DR+ Immature Cells Accumulates in the Blood Dendritic Cell Compartment of Patients with Different Types of Cancer

Abstract

Dendritic cell (DC) defects are an important component of immunosuppression in cancer. Here, we assessed whether cancer could affect circulating DC populations and its correlation with tumor progression. The blood DC compartment was evaluated in 136 patients with breast, prostate cancer and malignant glioma. Phenotypic, quantitative and functional analyses were performed at various stages of disease. Patients had significantly fewer circulating myeloid (CD11c+DC) and lymphoid (CD123+DC) DC, and a concurrent accumulation of CD11c-CD123- immature cells which expressed high levels of HLA-DR (DR+IC). Although DR+IC exhibited limited expression of markers ascribed to mature hematopoietic lineages, expression of HLA-DR, CD40 and CD86 suggested a role as antigen presenting cells. Nevertheless, DR+IC had a reduced capacity to capture antigen and elicited poor proliferation and IFN-?נsecretion by T-lymphocytes. Importantly, increased numbers of DR+IC correlated with disease status. Patients with metastatic breast cancer showed a larger number of DR+IC in the circulation than patients with local/nodal disease. Similarly, in patients with fully-resected glioma, the proportion of DR+IC in blood increased when evaluation indicated tumor recurrence. The reduction of blood DC correlating with the accumulation of a population of immature cells with poor immunological function may be associated with the increased immunodeficiency observed in cancer.