Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10915428 | Neoplasia | 2005 | 10 Pages |
Abstract
Dendritic cells (DC) have been implicated in the defective function of the immune system during cancer progression. We have demonstrated that patients with cancer have fewer myeloid (CD11c+) and plasmacytoid (CD123hi) DC and a concurrent accumulation of CD11câCD123â immature cells expressing HLA-DR (DR+IC). Notably, DR+IC from cancer patients have a reduced capacity to stimulate allogeneic T-cells. DR+IC are also present in healthy donors, albeit in smaller numbers. In this study, we assessed whether DR+IC could have an impact on the immune response by comparing their function with DC counterparts. For this purpose, DR+IC and DC were purified and tested in the presentation of antigens through major histocompatibility complex (MHC) II and MHC-I molecules. DR+IC were less efficient than DC at presenting antigens to T-cells. DR`IC induced a limited activation of T-cells, eliciting poor T-helper (Th) 1 and preferentially inducing Th2-biased responses. Importantly, despite DR+IC's poor responsiveness to inflammatory factors, in samples from healthy volunteers and breast cancer patients, CD40 ligation induced phenotypic maturation and interleukin 12 secretion, in turn generating more efficient T-cell responses. These data underscore the importance of inefficient antigen presentation as a mechanism for tumor evasion and suggest an approach to improve the efficacy of DC-based immunotherapy for cancer.
Keywords
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Cancer Research
Authors
Alberto Pinzon-Charry, Tammy Maxwell, Sandro Prato, Colin Furnival, Chris Schmidt, José Alejandro López,