Emotions today seem to play a fundamental role. In fact, emotions make social interaction between individuals possible and it is thanks to them that communication processes develop and make dynamics ...of social integration possible. In this paper, emotions are analysed as transformative resources, whose strength appears almost revolutionary for the subject’s ability to act. Despite the widespread processes of individualization in contemporary society, the individual appears to be looking for new ties and new relationships not only in the emotional sphere but also in other contexts which, although elusive and difficult to identify, are crucial for social life. What are the new scenarios in which emotions manifest themselves? What kind of bonds are generated in the practices of social interaction nowadays? It is in this perspective we intend to investigate emotions such as altruism, solidarity, gratitude, empathy induced thanks to the commitment of the Tuscan Voluntary Association Auser Abitare Solidale.
TLR3 belong to the Toll-like receptors family, it is mainly expressed on immune cells where it senses pathogen-associated molecular patterns and initiates innate immune response. TLR3 agonist ...poly(I:C) was developed to mimic pathogens infection and boost immune system activation to promote anti-cancer therapy. Accordingly, TLR agonists were included in the National Cancer Institute list of immunotherapeutic agents with the highest potential to cure cancer. Besides well known effects on immune cells, poly(I:C) was also shown, in experimental models, to directly induce apoptosis in cancer cells expressing TLR3.
This review presents the current knowledge on the mechanism of poly(I:C)-induced apoptosis in cancer cells. Experimental evidences on positive or negative regulators of TLR3-mediated apoptosis induced by poly(I:C) are reported and strategies are proposed to successfully promote this event in cancer cells.
Cancer cells apoptosis is an additional arm offered by poly(I:C), besides activation of immune system, for the treatment of various type of cancer. A further dissection of TLR3 signaling would contribute to greater resolution of the critical steps that impede full exploitation of the poly(I:C)-induced apoptosis. Experimental evidences about negative regulator of poly(I:C)-induced apoptotic program should be considered in combinations with TLR3 agonists in clinical trials.
Like other body districts, lungs present a complex bacteria community. An emerging function of lung microbiota is to promote and maintain a state of immune tolerance, to prevent uncontrolled and not ...desirable inflammatory response caused by inhalation of harmless environmental stimuli. This effect is mediated by a continuous dialog between commensal bacteria and immune cells resident in lungs, which express a repertoire of sensors able to detect microorganisms. The same receptors are also involved in the recognition of pathogens and in mounting a proper immune response. Due to its important role in preserving lung homeostasis, the lung microbiota can be also considered a mirror of lung health status. Indeed, several studies indicate that lung bacterial composition drastically changes during the occurrence of pulmonary pathologies, such as lung cancer, and the available data suggest that the modifications of lung microbiota can be part of the etiology of tumors in lungs and can influence their progression and response to therapy. These results provide the scientific rationale to analyze lung microbiota composition as biomarker for lung cancer and to consider lung microbiota a new potential target for therapeutic intervention to reprogram the antitumor immune microenvironment. In the present review, we discussed about the role of lung microbiota in lung physiology and summarized the most relevant data about the relationship between lung microbiota and cancer.
Pulmonary immunological tolerance to inhaled particulates might create a permissive milieu for lung metastasis. Lung microbiota contribute to pulmonary tolerance; here, we explored whether its ...manipulation via antibiotic or probiotic aerosolization favors immune response against melanoma metastasis. In lungs of vancomycin/neomycin-aerosolized mice, a decrease in bacterial load was associated with reduced regulatory T cells and enhanced T cell and NK cell activation that paralleled a significant reduction of melanoma B16 lung metastases. Reduction of metastases also occurred in lungs transplanted with bacterial isolates from antibiotic-treated lungs. Aerosolized Lactobacillus rhamnosus strongly promoted immunity against B16 lung metastases as well. Furthermore, probiotics or antibiotics improved chemotherapy activity against advanced B16 metastases. Thus, we identify a role for lung microbiota in metastasis and show that its targeting via aerosolization is a therapy that can prevent metastases and enhance responses to chemotherapy.
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•Aerosolized antibiotic reduces lung microbiota and a tolerogenic microenvironment•Aerosol delivery of an antibiotic or probiotic decreases tumor seeding in the lung•Antibiotic or probiotic aerosol improves chemotherapy against experimental metastases
Le Noci et al. reveal that modulation of pulmonary microbiota by antibiotic or probiotic aerosolization decreases tumor growth in the lung. Antibiotic treatment induces a reduction of immunosuppressive cells in the lung, while probiotic administration promotes maturation of resident antigen-presenting cells.
Adipose tissue contains multipotent elements with phenotypic and gene expression profiles similar to human mesenchymal stem cells (hMSCs) and pericytes. The chance of clinical translation of the ...multilineage potential of these cells is delayed by the poor/negligible cell survival within cryopreserved lipoaspirates, the difficulty of ex vivo expansion, and the complexity of current Good Manufacturing Practice (cGMP) requirements for expanded cells. Hence, availability of a minimally manipulated, autologous, hMSC/pericyte-enriched fat product would have remarkable biomedical and clinical relevance. Here, we present an innovative system, named Lipogems, providing a nonexpanded, ready-to-use fat product. The system uses mild mechanical forces in a completely closed system, avoiding enzymes, additives, and other manipulations. Differently from unprocessed lipoaspirate, the nonexpanded Lipogems product encompasses a remarkably preserved vascular stroma with slit-like capillaries wedged between adipocytes and stromal stalks containing vascular channels with evident lumina. Immunohistochemistry revealed that Lipogems stromal vascular tissue included abundant cells with pericyte/hMSC identity. Flow cytometry analysis of nonexpanded, collagenase-treated Lipogems product showed that it was comprised with a significantly higher percentage of mature pericytes and hMSCs, and lower amount of hematopoietic elements, than enzymatically digested lipoaspirates. Differently from the lipoaspirate, the distinctive traits of freshly isolated Lipogems product were not altered by cryopreservation. Noteworthy, the features of fresh product were retained in the Lipogems product obtained from human cadavers, paving the way to an off-the-shelf strategy for reconstructive procedures and regenerative medicine. When placed in tissue culture medium, the Lipogems product yielded a highly homogeneous adipose tissue-derived hMSC population, exhibiting features of hMSCs isolated from other sources, including the classical commitment to osteogenic, chondrogenic, and adipogenic lineages. Moreover, the transcription of vasculogenic genes in Lipogems-derived adipose tissue hMSCs was enhanced at a significantly greater extent by a mixture of natural provasculogenic molecules, when compared to hMSCs isolated from enzymatically digested lipoaspirates.
Immune checkpoint inhibitors (ICIs) have made a breakthrough in the treatment of different types of tumors, leading to improvement in survival, even in patients with advanced cancers. Despite the ...good clinical results, a certain percentage of patients do not respond to this kind of immunotherapy. In addition, in a fraction of nonresponder patients, which can vary from 4 to 29% according to different studies, a paradoxical boost in tumor growth after ICI administration was observed: a completely unpredictable novel pattern of cancer progression defined as hyperprogressive disease. Since this clinical phenomenon has only been recently described, a universally accepted clinical definition is lacking, and major efforts have been made to uncover the biological bases underlying hyperprogressive disease. The lines of research pursued so far have focused their attention on the study of the immune tumor microenvironment or on the analysis of intrinsic genomic characteristics of cancer cells producing data that allowed us to formulate several hypotheses to explain this detrimental effect related to ICI therapy. The aim of this review is to summarize the most important works that, to date, provide important insights that are useful in understanding the mechanistic causes of hyperprogressive disease. Keywords: Hyperprogressive disease, Immune checkpoint inhibitors, Immunotherapy, Immune-mediated mechanisms
The prognostic value of Toll-like receptor 3 (TLR3) is debated in cancer, differing between tumor types, methods, and cell types. We recently showed for the first time that TLR3 expression on early ...stage non-small-cell lung cancer (NSCLC) results associated with a good prognosis. Here, we provide experimental evidences explaining the molecular reason behind TLR3's favorable prognostic role. We demonstrated that TLR3 activation in vitro induces apoptosis in lung cancer cell lines and, accordingly, that TLR3 expression is associated with caspase-3 activation in adenocarcinoma NSCLC specimens, both evaluated by immunohistochemistry. Moreover, we showed that TLR3 expression on cancer cells contributes to activate the CD103+ lung dendritic cell subset, that is specifically associated with processing of antigens derived from apoptotic cells and their presentation to CD8+ T lymphocytes. These findings point to the relevant role of TLR3 expression on lung cancer cells and support the use of TLR3 agonists in NSCLC patients to re-activate local innate immune response.
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