1,721,045 research outputs found
Role of plasmacytoid dendritic cells in lung-associated inflammation.
No full textPlasmacytoid Dendritic Cells (pDCs) are important immune orchestrators. One of the most important features of pDCs is the high production of IFN type I that can promote the polarization of T cells towards a Th1 phenotype. Recent evidence has highlighted the relevance of pDCs in therapy for asthma, lung infections and cancer. However, it is to note that pDCs can also participate in suppressive networks via the recruitment of T regulatory cells. Further studies are needed to understand pDCs activity in the lung, not only to elucidate pathological mechanisms, but also to lead towards new therapeutic approaches for lung inflammatory-based diseases. The article also outlines recent patents on plasmacytoid DCs
The adenosinergic system in cancer: Key therapeutic target
No full textHigh amounts of adenosine are released in the tumor mass. Depending on the levels of adenosine, as well as on the receptor subtypes that are expressed by immune cells, adenosine can affect tumor growth in different fashions. Specifically targeting CD73, the rate-limiting enzyme for the extracellular generation of adenosine, or the A3 receptor offers new therapeutic strategies to limit tumor progression
Adenosine A2a receptor agonists as regulators of inflammation: pharmacology and therapeutic opportunities
No full textA2a receptor (A2aR) plays an important role in the regulation of inflammatory and immune responses. The activation of PKA-dependent and/or -independent pathways are responsible for the downmodulation of inflammatory networks and tissue injury. Based on promising recent studies, selective A2aR agonists are under clinical investigations for a wide range of disorders, such as ischemia-reperfusion injury, chronic inflammation, and infectious diseases. Nevertheless, further studies are required to improve our understanding in the ability of A2a receptor agonists to reduce tissue damage during inflammation. Characterization of A2aR-induced signaling pathways will be useful for the development of novel therapeutic strategies in inflammatory/immune diseases
Role of Plasmacytoid Dendritic Cells in Cancer
No full textIn the last decade several studies provided evidence that plasmacytoid dendritic cells (pDCs) actively participate in a wide spectrum of human diseases including infection, autoimmunity, and cancer. In particular, human neoplasms are populated by pDCs which presence is related to a poor prognosis. However, the role of tumor-associated pDCs (TApDCs) remains controversial. Various studies indicate that pDCs play an immunosuppressive role and facilitate tumor progression in both animal models and humans. In contrast, others found that the presence of activated pDCs results in tumor regression in mice. Given these findings, it is clear that pDC function plays a critical role in tumor biology. Understanding pDC biology in cancer represents an important necessity and will pave the road to novel therapeutic strategies to fight malignancies. In this chapter we will discuss novel findings about the therapeutic tools which are based on the pharmacological manipulation of tumor-associated pDCs
Inflammasome: Cancer's friend or foe?
No full textHigh serum concentrations of IL-1β and IL-18 are correlated to malignancies with low-rate survival from the time of diagnosis. The multimeric complex of the inflammasome is responsible for IL-1β/IL-18 synthesis/release. A number of endogenous (damage-associated molecular patterns) and exogenous (pathogen-associated molecular patterns) stimuli can provide signals for inflammasome activation in cancer. These stimuli can behave as tumor promoters via inducing chronic inflammation that, rather than providing a protective response to loss of tissue homeostasis, aberrantly facilitates tumor development. This view is contrasted in animal models of colon cancer in which the activation of some inflammasome complexes is associated with tumor protection. More studies are needed to understand the biology of the inflammasome in cancer and explore its therapeutic potential
Plasmacytoid Dendritic Cells Contribute to Doxorubicin-induced Tumor Arrest in a Mouse Model of Pulmonary Metastasis.
Full text linkThe biology of plasmacytoid dendritic cells (pDCs) in tumors is an emerging area of investigation. pDCs populate many human solid tumors, including lung cancer. The aim of our study was to understand the role of pDCs in pulmonary metastases during the treatment with conventional antitumor agents. For this purpose, C57Bl/6 mice were inoculated with the metastatic cell line B16-F10 or B16-Flt3L cells. The administration of doxorubicin significantly reduced the amount of pulmonary metastases in both experimental models. It is interesting to note that, 5 hours after injection, doxorubicin-induced tumor cell death was associated with higher influx of pDCs to the lung, which at 24 hours populated the mediastinal lymph nodes. In this context, lung tumor-derived pDCs obtained from mice treated with doxorubicin had higher levels of MHC I and MHC II that well correlated with the higher proliferation rate of CD4 and CD8 T cells, compared with PBS mice. Siglec-H and PD-L1 levels were not altered on lung tumor-associated pDCs derived from doxorubicin-treated and PBS-treated mice. In addition, lung tumor-associated pDCs obtained from mice treated with doxorubicin released higher levels of granzyme B. The administration of 2 consecutive doses of doxorubicin in lung tumor-bearing mice showed that B16-Flt3L-implanted mice had lower tumor burden than B16-F10-implanted mice. In conclusion, our data highlight the crucial role of the proinflammatory pDCs for the adaptive antitumor immunity. Strategies aiming at modulating pDC phenotype and activity in the tumor site might prove to be novel and effective, enhancing the conventional/actual antitumor strategies
Plasmacytoid dendritic cells and their therapeutic activity in cancer.
Full text linkIn the last decade several studies provided evidence that plasmacytoid dendritic cells (pDCs) infiltrate human neoplasms with poor prognosis. However, the role of tumor-associated pDCs remains controversial. Various studies indicate that pDCs play an immuno-suppressive role and facilitate tumor progression in both animal models and humans. In contrast, others found that the presence of activated tumor-associated pDCs results in tumor regression in mice. Given these findings, understanding pDC function in tumor biology is an important necessity and may pave the way for novel therapeutic strategies to fight malignancies
Drug resistance in non-small cell lung Cancer (NSCLC): Impact of genetic and non-genetic alterations on therapeutic regimen and responsiveness
No full textThe discovery of genetic alterations, that can be targeted therapeutically, has launched a new era for lung cancer research and personalized therapy. However, not all the identified new genetic driver mutations are therapeutically targetable due to high toxicity profile. On the other hand, those genetic alterations that could be pharmacologically targeted, are often subject of alternative mutations that lead to drug resistance, which represents one of the major clinical limitation. Mechanisms of acquired resistance in oncogene-driven malignancies occur after additional genetic alterations of the primary oncogene. In this scenario, the secondary genetic alteration can lead to up-regulation of bypass-signaling pathways, changes in tumor histology or alterations in drug metabolism, that are able to promote drug resistance with an ensuing lower survival rate of the patient. Another aspect to be considered is that non-genetically mutated patients still have poor pharmacological options and therefore still represent an unmet medical need. Therefore, identifying mechanisms underlying both drug resistance in genetically mutated patients and novel therapeutic alternatives for non-mutated NSCLC patients is still an area of intense investigation
Innate Immunity, Toll-like Receptors, and Atherosclerosis: mouse models and methods.
No full textChronic inflammation and aberrant lipid metabolism represent hallmarks of atherosclerosis. Innate immunity critically depends upon Toll-like receptor (TLR) signalling. Recent data directly implicate signalling by TLR4 and TLR2 in the pathogenesis of atherosclerosis. The role that TLRs play in the pathogenesis of atherosclerosis can be assessed by using several animal models, which provide a double genetic deficiency in TLRs and molecules implicated in the lipid metabolism, such as ApoE or LDL receptor. Furthermore, a more recent technique, such as the bone marrow transplantation (BMT), can be a useful and straightforward method to elucidate the role of stromal versus hematopoietic cells in the acceleration of the atheroma
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