Dendritic cell tumor killing activity and its potential applications in cancer immunotherapy

Abstract

Universally viewed as the sentinels and messengers of the immune system and traditionally referred to as professional antigen-presenting cells, dendritic cells (DCs) play a fundamental role in antitumor immunity. DCs are uniquely equipped with the ability to acquire, process, and present to T lymphocytes tumor-derived antigens. They can drive the differentiation of naive T cells into activated tumor-specific effector lymphocytes. DCs also dictate the type and regulate the strength and duration of T-cell responses. In addition, they contribute to natural killer and natural killer T-cell antitumoral function and to B-cell-mediated immunity. Besides this cardinal role as orchestrators of innate and adaptive immune responses, many studies have provided evidence that DCs can also function as direct cytotoxic effectors against tumors. This less conventional aspect of DC function has, however, raised controversy as it relates to the origin of these cells and the induction, regulation, and mechanisms underlying their tumoricidal activity. The possible impact of the cytotoxic function of DCs on their capability to present antigens also has been the focus of intensive research. This review examines these questions and discusses the biological significance of this nontraditional property and possible strategies to exploit the killing potential of DCs in cancer immunotherapy.

Fig. 1. The multifaceted role of KDC in cancer immunoediting

The cytotoxic function of KDC may promote the release and subsequent acquisition of tumor-derived antigens during the first steps of the elimination process. After maturation, KDC can switch function and present processed cancer antigens to tumor-specific CD4⁺ or CD8⁺ leading to their clonal expansion and activation. KDC may also contribute to the equilibrium phase by producing RNI and ROS which may exacerbate the mutational potential of malignant cells and foster the emergence of new populations of immune escape variants. During the escape stage, immature KDC may take advantage of their killing activity to gather cancer antigens. These KDC, impaired in their maturation by the immunosuppressive environment may trigger the anergy or apoptosis of T lymphocytes or promote the generation of suppressive Treg.