Plasmacytoid dendritic cells and cancer

Abstract

Cancer develops in a complex microenvironment comprising cancer cells, stromal cells, and host immune cells with their soluble products. The counteracting host-protective and tumor-promoting roles of different immune cell populations have been elegantly clarified in the last decade by pertinent genetically modified mouse models. Among cells with a potential role in cancer immunity, PDCs might represent important players as a result of their capacity to bring together innate and adaptive immunity. This review summarizes current knowledge about the role of PDCs in cancer immunity. PDCs have been documented in primary and metastatic human neoplasms; however, the clinical significance of this finding is still unknown. Once into the tumor bed, PDCs can be hijacked by the tumor microenvironment and lose their propensity to produce the required amount of endogenous I-IFN. However, when properly reprogrammed (i.e., by TLR agonists), PDCs might mediate tumor rejection in a clinical setting. Tumor rejection, at least partially, is driven by I-IFN and seems to require a cross-talk with other innate immune cells, including IFN DCs. The latter evidence, although still limited to skin cancers, can provide a leading model for developing adjuvant immune therapy for other neoplasms. To this end, the generation of appropriate mouse models to modulate the frequency and activation state of murine PDCs will also be of remarkable importance.

slanDCs selectively accumulate in carcinoma-draining lymph nodes and marginate metastatic cells

“…By contrast, pDCs from the same patient cohort were significantly reduced in number, not only in an age-dependent but also in a cancer-related manner (Fig. 9c), in line with published observations 31,34,[37][38][39] . Concomitantly, we also found that either the ability to ingest tumour cell-derived apoptotic bodies (Fig.…”

“…By contrast, the capacity of CCR-derived pDCs to produce IFNa upon CpG stimulation was partially defective (Fig. 9f), as largely documented in patients with other carcinoma types 34,40,41 . Significantly, number and function (for example, cytokine production) of the slanDC contingent was maintained even in advanced disease stages (Fig.…”

“…More importantly, by analysing circulating slanDCs from a cohort of patients with advanced CCR, we found that the slanDC compartment, unlike pDCs from the same patient cohort, remains substantially intact in terms of number and responsive to stimuli in terms of cytokine (TNFa and IL-12p70) production, induction of T-cell proliferation as well as gene expression profile by microarray analysis, even in advanced stage disease. Thus, in contrast to other DC subsets 7,34 Tissue microarray preparation. Three tissue microarray (TMA) blocks were prepared from a series of 126 PCs from different sites, as detailed in Supplementary Table S1.…”

“…We also observed that the uptake of tumour-cell-derived apoptotic bodies by slanDCs is Dectin-1/CLEC7A-and CD18-independent, and that IFNg-activated slanDCs cultured with fluorescent-labelled, alive HT29 cells contained intracellular apoptotic bodies likely derived from the slanDC-mediated killing of HT29 cells, as previously shown 16 . Circulating mDCs and pDCs from cancer patients are frequently reduced in number and functionally defective [30][31][32][33][34] . Recent works have proved the prognostic significance of the immune response to colon carcinomas (CCR) 35,36 .…”

Plasmacytoid Dendritic Cells Play a Key Role in Tumor Progression in Lipopolysaccharide-Stimulated Lung Tumor–Bearing Mice

“…pDCs have been found in many human solid tumors, including lung cancer, and correlates to a poor patient prognosis (29). They are present in their nonactivated state and have been associated with the development and maintenance of the immunosuppressive tumor microenvironment (30).…”