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 (DC) play a fundamental role in antitumor immunity. DC are uniquely equipped with the ability to acquire, process and present tumor-derived antigens to T lymphocytes. They can drive the differentiation of naïve T cells into activated tumor-specific effector lymphocytes. DC also dictate the type and regulate the strength and duration of T cell responses. In addition, they contribute to NK and NKT 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 DC can also function as direct cytotoxic effectors against tumors. This less conventional aspect of DC lifestyle 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 DC on their antigen presenting capability has also been the focus of intensive research. In this review, we examine these questions and discuss the biological significance of this non-traditionalproperty and possible strategies to exploit DC killing potential in cancer immunotherapy.

Modeling putative therapeutic implications of exosome exchange between tumor and immune cells

“…The two networks, however, differ from each other in the interactions between C and D. In case I (Fig. 1A), D directly kills C by exosomes (24) and/or some cytokines (52); C induces the D maturation by presenting tumor-associated antigens on the surface when the concentration of C is low (15,53), but inhibits D differentiation by exosomes and/or cytokines when the concentration of C is above a threshold level (33,54). The deterministic rate equations for the dynamics of C, D, and K densities are given by…”

The emerging roles of exosomes in leukemogeneis

“…Suppression of exosome production by indomethacin has been shown to increase chemotherapeutic sensitivities of B-cell lymphoma [70]. DCs present cancer cell antigens on MHC class I or class II to T cells to bring about cytotoxicity towards cancer cells [72]. DC mediated immunotherapy combined with chemotherapy produces the longest survival times in DBA2 mice bearing murine L1210 lymphocytic leukemia tumor [73].…”

Docosahexaenoic acid (DHA) promotes immunogenic apoptosis in human multiple myeloma cells, induces autophagy and inhibits STAT3 in both tumor and dendritic cells

“…DCs are at the center of the immune system owing to their ability to induce tumor-specific effector T cells, that can reduce the tumor mass and induce immunological memory to control tumor relapse, thus leading to long-term survival [26]. Therefore, DCs represent an essential target in efforts to generate therapeutic immunity against cancer, especially during chemotherapy [26, 27].…”

“…Therefore, DCs represent an essential target in efforts to generate therapeutic immunity against cancer, especially during chemotherapy [26, 27]. The capability to stimulate protective anticancer immune responses by DCs depends on multiple conditions and multiple strategies have been proposed.…”