The bromodomain and extra-terminal domain (BET) family inhibitors are small molecules that target the dysregulated epigenetic readers, BRD2, BRD3, BRD4 BRDT, at various transcription-related sites, including super-enhancers. BET currently under investigation both in pre-clinical cell culture tumor-bearing animal models, as well clinical trials. However, is case with other chemotherapeutic modal...

CTL are endowed with the ability to eliminate pathogens through perforin-mediated cytotoxic activity. The mechanism for perforin-mediated Ag-specific killing has been solely attributed to cytotoxic granule exocytosis from activated CD8(+) T cells. In this study, we redefine this mechanism, demonstrating that virus-specific CD8(+) T cells rapidly up-regulate perforin in response to stimulation t...

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Cytotoxic T-cell precursors have been shown to occur in spleens of 2-3-day-old mice. By 12 days after birth, the cytotoxic T-cell response of spleen cells to alloantigens has reached 23-32% of adult levels. Addition of extra T-helper cells did not permit cytotoxic T-cell development in spleen cells from newborn to 2-day-old mice suggesting either a lack of precursors or suppression of precursor...

Background Cytotoxic mechanisms are involved in most forms of drug-induced skin diseases, but till now only a small number of studies has been addressed the question whether in vitro detection of cytotoxic drug-specific response could be helpful in drug hypersensitivity diagnosis. The aim of this study was to assess and compare different cytotoxic tests as an alternative nonradioactive approach...

We investigated the feasibility of generating cytotoxic T cell clones against autologous human melanoma cells using a melanoma cell line (VIP) and a spontaneously transformed autologous fibroblast line (VIP-F:T). Cytotoxic lymphocytes (CL) generated against the VIP melanoma cells in one-way mixed lymphocyte-tumor cell interactions were expanded in interleukin 2 for 2 wk. The expanded CL were cl...

The role of the humoral and cellular arms of the immune response in protection against respiratory syncytial virus (RSV) infection and in the pathogenesis of the severe forms of this disease is poorly understood. The recent demonstration that some inbred mouse strains can be infected with RSV has opened the way to a detailed investigation of RSV immunity. We report here the finding of major his...

Cell-mediated cytotoxic (CMC) activity is the main cellular immunological response to kill tumor cells, virus-infected cells and parasites (Groscurth, 1989). In mammalian species this is carried out by several leucocyte populations depending on the non-specific/innate and specific/adaptive immune response. Among the last ones, the CMC activity is carried out by cytotoxic T lymphocytes (CTLs), e...

For several decades, cytotoxic chemotherapeutic agents were considered the basis of anticancer treatment for patients with metastatic tumors. A decrease in tumor burden, assessed by volumetric computed tomography and magnetic resonance imaging, according to the response evaluation criteria in solid tumors (RECIST), was considered as a radiological response to cytotoxic chemotherapies. In additi...

Vaccine-induced cytotoxic T lymphocytes (CTLs) play a critical role in adaptive immunity against cancers. An important goal of current vaccine research is to induce durable and long-lasting functional CTLs that can mediate cytotoxic effects on tumor cells. To attain this goal, there are four distinct steps that must be achieved. To initiate a vaccine-induced CTL antitumor immune response, dendr...