Colorectal cancer (CRC) results from the accumulation of both genetic and epigenetic alterations of the genome. However, also the formation of an inflammatory milieu plays a pivotal role in tumor development and progression. Dendritic cells (DCs) play a relevant role in tumor by exerting differential pro-tumorigenic and anti-tumorigenic functions, depending on the local milieu. Quantitative and functional impairments of DCs have been widely observed in several types of cancer, including CRC, representing a tumor-escape mechanism employed by cancer cells to elude host immunosurveillance.Understanding the interactions between DCs and tumors is important for comprehending the mechanisms of tumor immune surveillance and escape, and provides novel approaches to therapy of cancer. This review summarizes updated information on the role of the DCs in colon cancer development and/or progression.

Human aging is associated with immunosenescence, a process characterized by alterations in numerical and functional features of immune system components. Dendritic cells (DCs) are the main antigen-presenting cells, playing a pivotal role in adaptive and innate immunity. Therefore, we investigated the distribution of human circulating DCs throughout the life, in order to contribute to the knowledge of the physiological background underlying the aging of immune system. Cytofluorimetric analysis of peripheral blood samples by all-aged healthy population showed a significant decrease of circulating DCs and of their two main subsets among age. This reduction was limited to the plasmacytoid cell subtype when young and old subjects were analyzed separately. The analysis of circulating Treg cell number in a cohort of the subjects showed a significant reduction with increasing age and a positive significant correlation to myeloid or plasmacytoid absolute numbers. In conclusion, this work provides a large set of data of normal reference values of peripheral blood dendritic cells in healthy population suitable for comparative clinical studies concerning pathological immune dysfunctions.

SummaryExtracorporeal photopheresis (ECP) has been considered an efficient dendritic cell (DC) therapy, used for treating both T cell malignancy, as well as T cell-mediated diseases. During the ECP procedure leucocytes are exposed to photoactivable agent 8-methoxypsolaren (8-MOP) and ultraviolet (UV) A radiation (PUVA) prior to reinfusion. Despite its clinical efficacy the mechanism of action remains elusive. As it has been reported that ECP might promote the differentiation of monocytes into immature DCs, we investigated the effects of UVA light (2 J/cm 2 ) and 8-MOP (100 ng/ml) on in vitro monocyte-to-DC differentiation from normal donors. DCs were generated from human purified CD14 + cells. Because monocytes are killed by PUVA and taking into account that only 5-10% of circulating mononuclear cells are exposed to PUVA during the ECP procedure, we developed an assay in which 10% of PUVA-treated monocytes were co-cultured with untreated monocytes. We first demonstrate that the presence of 10% apoptotic cells and monocyte activation were not enough to induce monocyte differentiation into DCs. Adding cytokines to our culture system, we obtained immature DCs characterized by significantly higher phagocytic activity and human leucocyte antigen D-related (HLA-DR) expression. These DCs preserved the capacity to be activated by lipopolysaccharide, but showed a reduced capacity to induce allogeneic T cell proliferation when first co-cultured with 10% of PUVAtreated cells. Our experimental design provides a novel insight into the real action of 8-MOP and UVA light on dendritic cell biology, suggesting an additional mechanism by which 8-MOP and UVA light exposure may influence immune responses.

The natural history of the immune thrombocytopenia (ITP) is interesting and intriguing because it traces different steps underlying autoimmune diseases. The review points out the main steps that have accompanied the stages of its history and the consequential changes related to its terminology. ITP is an autoimmune disease resulting from platelet antibody-mediated destruction and impaired megakaryocyte and platelet production. However, research advances highlight that a complex dysregulation of the immune system is involved in the pathogenesis of this condition. The review examines the role of the multiple immune components involved in the autoimmunity process, focusing on the more recent mechanisms, which could be new promising therapeutic targets for ITP patients.

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Mesenchymal stem cells (MSCs) represent a promising source of progenitor cells having the potential to repair and to regenerate diseased or damaged skeletal tissues. Bone marrow (BM) has been the first source reported to contain MSCs. However, BM-derived cells are not always acceptable, due to the highly invasive drawing and the decline in MSC number and differentiative capability with increasing age. Human umbilical cord blood (UCB), obtainable by donation with a noninvasive method, has been introduced as an alternative source of MSCs. Here human UCB-derived MSCs isolation and morpho-functional characterization are reported. Human UCB-derived mononuclear cells, obtained by negative immunoselection, exhibited either an osteoclast-like or a mesenchymal-like phenotype. However, we were able to obtain homogeneous populations of MSCs that displayed a fibroblast-like morphology, expressed mesenchym-related antigens and showed differentiative capacities along osteoblastic and early chondroblastic lineages. Furthermore, this study is one among a few papers investigating human UCB-derived MSC growth and differentiation on three-dimensional scaffolds focusing on their potential applications in regenerative medicine and tissue engineering. UCB-derived MSCs were proved to grow on biodegradable microfiber meshes; additionally, they were able to differentiate toward mature osteoblasts when cultured inside human plasma clots, suggesting their potential application in orthopedic surgery.

Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths in Western countries. Today, the role of the host’s immune system in controlling the progression and spread of solid tumors is broadly established. Tumor immunosurveillance escape mechanisms, such as those involving dendritic cells (DCs), the most important antigen-presenting cells, are likewise recognized processes involved in cancer. The present study evaluates the ability of CRC patients to generate DCs in vitro from circulating monocytes at both pre- and post-operative timepoints; the results are correlated with the stage of disease to shed light on the systemic immune statuses of CRC patients. Our data showed that patients’ DCs had lower co-stimulatory molecule expression and were less able to present antigens to allogeneic T cells compared to healthy controls’ (HC) DCs. Furthermore altered cytokine secretion, such as increased IL-10 and reduced IL-12 and TNF-α, was observed. At the post-operative timepoints we observed a recovery of the patients’ ability to generate immature DCs, compared to HCs, but the maturational capacity remained affected. Our study conclusively highlights the persistently impaired in vitro generation of fully mature and functional DCs, which appears to be more altered during advanced stages. This work sheds light on a dendritic cell-based tumor immune escape mechanism that could be useful for the development of more effective immunotherapeutic strategies.

Abnormalities in the immune system and zinc homeostasis in patients with β-thalassemia major (TM) have been reported. Since zinc ion is essential for the efficiency of the immune system and is required to induce biological activity to thymulin (Zn-FTS), a biochemically defined thymic hormone, we investigated the plasma levels of zinc and both active thymulin (Zn-FTS) and total zinc saturable thymulin (Zn-FTS+FTS) in 18 patients with TM aged between 2 and 31 years and 22 normal controls of the same age. Inhibitory molecules anti-thymulin and the distribution of lymphocyte subsets were also analyzed. Patients with TM presented significantly lowered plasma zinc and thymulin levels when compared to normal subjects. The significant enhancement of the active form of the hormone after zinc addition in vitro suggests that low thymulin values found in TM are due not to a thymic failure in synthesizing and secreting the thymic hormone, but a defect in zinc saturation of the hormone. An impairment of cell subset distribution was also demonstrated. This study shows that zinc and thymulin deficiency contribute to the complex mechanisms underlying immune dysfunction in TM.