Peripheral T-cell proliferative disease/lymphoma is a group of diseases which exhibits heterogeneity in clinical manifestations, pathological ®ndings and outcomes. They are highly associated with the Epstein-Barr virus (EBV) infection. It is likely that EBV plays an important role in the tumorigenesis. From January 1997 through April 2000, we identi®ed 100 patients. One hundred healthy age-and sex-matched controls were selected. Serologic tests for the EBV infection and the study of EBV genomes in circulating non-T cells (CD3 ± cells), T cells (CD3 + cells), and T-cell subsets (CD4 + and CD8 + cells) were performed. The main features were prolonged fever, weight loss, hepatosplenomegaly, lymphadenopathy, multiorgan involvement, anemia, and high serum alkaline phosphatase and lactate dehydrogenase. Fifty-one patients had an aggressive course and died; median survival was 21 months. Chemotherapy was not effective in improving survival. Anti-viral capsid antigen-IgG and anti-early antigen-IgG were signi®cantly elevated, whereas there was no signi®cant difference in anti-EBV nuclear antigen. EBV internal repeat-1 region (IR-1) in the peripheral blood CD3 + cells was detected in 65% of the patients but in none of the controls. For the CD3 ± cells, EBV IR-1 was detected in 88% of the patients and 50% of the controls. Among twenty-®ve patients whose CD3 + cells were positive for EBV IR-1, 6 (24%) showed EBV IR-1 in only CD4 + cells, 6 (24%) in only CD8 + cells, and 13 (52%) in both CD4 + and CD8 + cells. The 30-bp deletion variant of the EBV latent membrane protein-1 gene was signi®cantly higher in the patients than in the controls. These data support the chronic infective process. The EBV which is dormant in non-T cells may infect T cells and contribute to the pathogenesis of disease in a select group of patients. Am.
Providing an external mechanical stress to cancer cells seems to be an effective approach to treat cancer locally. Numbers of reports on cancer cell death subjected to mechanical stress loading are increasing, but they are more focused on apoptosis. Inducing necrosis is also important in attracting more immune cells to the cancer site via the release of danger-associated molecular patterns from cancer cells. Here we applied dynamic compression to breast cancer cells with a low frequency (0.1–30 Hz) and for a short duration (30–300 s) and they resulted in a mixed mode of apoptosis and necrosis dominant with necrotic cell death, which we call mechanical stress-induced cell death (MSICD). The necrotic cell damage of mechanically treated breast cancer cells increased in a force-dependent and time-dependent manner while a trend of frequency-independent MSICD was observed.
Purpose
Most studies characterizing antitumor properties of iNKT cells have used the agonist, α-galactosylceramide (α-GalCer). However, α-GalCer induces strong, long-lasting anergy of iNKT cells, which could be a major detriment for clinical therapy. A novel iNKT cell agonist, β-mannosylceramide (β-ManCer), induces strong antitumor immunity through a mechanism distinct from that of α-GalCer. The objective of this study was to determine whether β-ManCer induces anergy of iNKT cells.
Experimental design
Induction of anergy was determined by ex vivo analysis of splenocytes from mice pre-treated with iNKT cell agonists as well as in the CT26 lung metastasis in vivo tumor model.
Results
β-ManCer activated iNKT cells without inducing long-term anergy. The transience of anergy induction correlated with a shortened duration of PD-1 upregulation on iNKT cells activated with β-ManCer, compared with α-GalCer. Moreover, while mice pretreated with α-GalCer were unable to respond to a second glycolipid stimulation to induce tumor protection for up to two months, mice pretreated with β-ManCer were protected from tumors by a second stimulation equivalently to vehicle-treated mice.
Conclusions
The lack of long-term functional anergy induced by β-ManCer, which allows for a second dose to still give therapeutic benefit, suggests the strong potential for this iNKT cell agonist to succeed in settings where α-GalCer has failed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.