Abstract
Many clinical trials have been carried out or are in progress to assess the therapeutic potential of dendritic-cell- (DC-) based vaccines on cancer patients, and recently the first DC-based vaccine for human cancer was approved by the FDA. Herewith, we describe the general characteristics of DCs and different strategies to generate effective antitumor DC vaccines. In recent years, the relevance of the tumor microenvironment in the progression of cancer has been highlighted. It has been shown that the tumor microenvironment is capable of inactivating various components of the immune system responsible for tumor clearance. In particular, the effect of the tumor microenvironment on antigen-presenting cells, such as DCs, does not only render these immune cells unable to induce specific immune responses, but also turns them into promoters of tumor growth. We also describe strategies likely to increase the efficacy of DC vaccines by reprogramming the immunosuppressive nature of the tumor microenvironment.
Highlights
Dendritic cells (DCs) are professional antigen-presenting cells (APCs) found in peripheral tissues and in immunological organs such as the thymus, bone marrow, spleen, lymph nodes, and Peyer’s patches [1,2,3]
Recent reports indicate that BDCA3+ DCs might be the putative homologues of murine CD8α+ DCs due to their expression of Toll-like receptors (TLRs)-3, baft3 [60], and XCR1 [16, 17, 61], their capability of producing IL12 upon stimulation [60], and their higher capability of cross-presenting antigen when compared to CD16+ and BDCA1+ DCs [60,61,62]
Several reports indicate that DC vaccines are able to induce immune responses in cancer patients, they have only rarely resulted in objective clinical responses based on the response evaluation criteria in solid tumors (RECISTs) and no indication or evidence has been obtained that DC vaccines represent a method of stimulating protective immunity in cancer patients that is superior to other vaccination strategies [121]
Summary
Dendritic cells (DCs) are professional antigen-presenting cells (APCs) found in peripheral tissues and in immunological organs such as the thymus, bone marrow, spleen, lymph nodes, and Peyer’s patches [1,2,3] Their function is to scan peripheral tissues where they recognize, take up and process pathogens and present pathogen-derived antigenic peptides in the context of major histocompatibility molecules (MHCs) to naive T lymphocytes at lymphoid organs [4, 5]. Through these processes, DCs form a critical link between innate and adaptive immunity and are essential for the development of antigen-specific immune responses. Some of the main PRRs active in innate immunity include Toll-like receptors (TLRs) and NOD-like receptors (NLRs) [6, 7]
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