The Crosstalk Between Dendritic Cells, Cytokine-Induced Killer Cells And Cancer Cells From The Perspective Of Combination Therapy

Abstract

Dendritic cells (DCs) are considered the most potent professional antigen-presenting cells (APCs) that elicit adaptive antitumour immunity. DCs integrate multiple environmental signals by efficiently processing tumour-associated antigens (TAAs) and migrating to draining lymph nodes (dLNs), where they present foreign antigens to T cells for priming. DCs thus serve as a major link between innate and adaptive immunity. Although DCs (mostly monocyte-derived DCs [mo-DCs]) have already been used in cancer therapies, such approaches have shown limited efficacy. Mo-DCs have the unique ability to present antigens to T cells in peripheral tissues. CD3+CD56+ cytokine-induced killer (CIK) cells are characterized by both MHC-restricted and MHC-unrestricted antitumour cytotoxicity against a broad range of cancer cells. This review presents an overview of the mechanisms by which mo-DCs and CIK cells’ interact with each other and with tumours. The maturation of DCs was identified as a crucial step in the development of effective DC-based vaccines against cancer. A further improved adoptive immunotherapy strategy involves a combination of mature mo-DCs and CIK cells. Combination therapy presents many opportunities for cancer treatment, as reported by a number of clinical trials. However, there is a lack of fundamental studies on the interaction of in vitro-generated mo-DCs with CIK cells. We discuss several methods of boosting DC-based vaccines and review the current knowledge of contact-dependent and cytokine-induced interactions of mo-DCs with CIK cells. We highlight that the combination of mo-DCs with CIK cells activates MHC-restricted and MHC-unrestricted immune responses.