Dendritic cell defects in patients with cancer: mechanisms and significance

Dendritic cells (DCs) are the most potent antigen-presenting cells and are uniquely capable of stimulating primary immune responses by the presentation of antigen in the context of high levels of costimulatory molecule expression [1,2]. The functional characteristics of DCs evolve with their stage of maturation. Immature DCs are found at sites of antigen capture and excel at antigen processing, but lack significant stimulatory capacity. After antigen uptake, DCs undergo further differentiation characterized by the loss of phagocytic capacity and increased expression of costimulatory molecules necessary for T cell activation. DC-based tumor vaccines are being explored as tumor immunotherapy. One approach involves the introduction of tumor-associated antigens or genes that are subsequently taken up by native DCs, which then migrate to the draining lymph node. An alternative strategy involves the administration of DCs manipulated ex vivo to express tumor antigens [3-7].DCs isolated from cancer patients exhibit quantitative and functional deficiencies [8-11]. Decreased numbers of mature DCs have been demonstrated in the tumor bed, draining lymph nodes, and circulation in multiple tumor models. In patients with head and neck squamous cell carcinoma (HNSCC), numbers of DCs were halved in early-stage patients, with a further decrease in patients with more advanced disease [10]. DC subset analysis in patients with breast cancer and HNSCC has revealed that decreases in cell numbers are confined to DCs of the myeloid in comparison with those of the plasmacytoid or lymphoid lineage. Surgical debulking of breast and prostate cancer results in a corresponding increase in myeloid-derived DCs [10,12]. Minimal DCs are recruited to the tumor bed in patients with renal and prostate cancer. Those present have low levels of costimulatory molecules and a decreased capacity to stimulate allogeneic T cell proliferation [11,13]. Similarly, DCs isolated from patients with colon cancer lack