Pathogen-Associated Molecular Patterns Induced Crosstalk between Dendritic Cells, T Helper Cells, and Natural Killer Helper Cells Can Improve Dendritic Cell Vaccination

Abstract

A coordinated cellular interplay is of crucial importance in both host defense against pathogens and malignantly transformed cells. The various interactions of Dendritic Cells (DC), Natural Killer (NK) cells, and T helper (Th) cells can be influenced by a variety of pathogen-associated molecular patterns (PAMPs) and will lead to enhanced CD8+ effector T cell responses. Specific Pattern Recognition Receptor (PRR) triggering during maturation enables DC to enhance Th1 as well as NK helper cell responses. This effect is correlated with the amount of IL-12p70 released by DC. Activated NK cells are able to amplify the proinflammatory cytokine profile of DC via the release of IFN-γ. The knowledge on how PAMP recognition can modulate the DC is of importance for the design and definition of appropriate therapeutic cancer vaccines. In this review we will discuss the potential role of specific PAMP-matured DC in optimizing therapeutic DC-based vaccines, as some of these DC are efficiently activating Th1, NK cells, and cytotoxic T cells. Moreover, to optimize these vaccines, also the inhibitory effects of tumor-derived suppressive factors, for example, on the NK-DC crosstalk, should be taken into account. Finally, the suppressive role of the tumor microenvironment in vaccination efficacy and some proposals to overcome this by using combination therapies will be described.

Significance of Frequencies, Compositions, and/or Antileukemic Activity of (DC-stimulated) Invariant NKT, NK and CIK Cells on the Outcome of Patients With AML, ALL and CLL

“…Recently, details about the mechanisms behind the increase of antitumor-reactivity (eg, pathogen-associated molecular patterns or cytokines) have been detected. 39,43 Moreover cytokines, cellular factors, antibodies promote NK cell activations, and DC-NK crosstalk establishing a microenvironment which enables antitumor reactions. 44,45 Moreover, a crosstalk between CIK cells and DC has been reported recently, demonstrating an influence of a DC stimulation on the phenotype as well as antileukemic cytotoxicity of CIK cells.…”

“…39,43 Mature DCs are known to produce IL-12 stimulating iNKT cells to increase IFN-g release coactivating NK cells and their production of IFN-g, 39 what could in return lead to a release of pro-inflammatory cytokines by DC. 43 Our preliminary data obtained with some cases in part confirm these findings: increased release of cytokines (IL-17A, IL-10) correlated with achieved "lysis"/antitumor activity and with higher iNKT, NK and CIK cell frequencies-pointing to a cytokine-mediated antitumor activity. 39 Moreover, we could show that "highest" iNKT cell frequencies were correlated with higher DC-pointing to a coactivation between iNKT cells and DC.…”

Dendritic cell targeted HIV‐1 gag protein vaccine provides help to a recombinant Newcastle disease virus vectored vaccine including mobilization of protective CD8+ T cells

“…On the other hand the contribution of CD4 þ T cells to the CPB strategy are numerous including our previous report [22] and several other findings demonstrating the usefulness of helper CD4 þ T cells in T cell immunity [22,32,43] (reviewed in Ref. [53,54]).…”

Murine hepatoma treatment with mature dendritic cells stimulated by Trichinella spiralis excretory/secretory products

“…Mature DCs are correlated with an immune contexture characterized by TH1 polarization, infiltration by effectors cells (T cells, NK cells, and plasma cells) and cytotoxic effector functions [ 36 , 40 ]. Mature DCs play a critical role in coordinating cellular interplay and in the anti-tumor immunity in host defense against pathogens and malignantly transformed cells [ 10 , 17 – 19 , 25 , 30 , 32 ]. Pathogen-derived products have the ability to induce the maturation of bone marrow-derived dendritic cells (BMDCs) [ 12 ].…”