Tumour-derived extracellular vesicles (EVs) are of increasing interest as a resource of diagnostic biomarkers. However, most EV assays require large samples, are time-consuming, low-throughput and costly, and thus impractical for clinical use. Here, we describe a rapid, ultrasensitive and inexpensive nanoplasmon-enhanced scattering (nPES) assay that directly quantifies tumor-derived EVs from as little as 1 μL of plasma. The assay uses the binding of antibody-conjugated gold nanospheres and nanorods to EVs captured by EV-specific antibodies on a sensor chip to produce a local plasmon effect that enhances tumour-derived EV detection sensitivity and specificity. We identified a pancreatic cancer EV biomarker, ephrin type-A receptor 2 (EphA2), and demonstrate that an nPES assay for EphA2-EVs distinguishes pancreatic cancer patients from pancreatitis patients and healthy subjects. EphA2-EVs were also informative in staging tumour progression and in detecting early responses to neoadjuvant therapy, with better performance than a conventional enzyme-linked immunosorbent assay. The nPES assay can be easily refined for clinical use, and readily adapted for diagnosis and monitoring of other conditions with disease-specific EV biomarkers.

IL-17-secreting CD8 T cells (Tc17) have been described in several settings, but little is known regarding their functional characteristics. While Tc1 cells produced IFN-γ and efficiently killed targets, Tc17 cells lacked lytic function in vitro. Interestingly, the small numbers of IFN-γ-positive or IL-17/IFN-γ-double-positive cells generated under Tc17 conditions also lacked lytic activity and expressed a similar pattern of cell surface proteins to IL-17-producing cells. As is the case for Th17 (CD4) cells, STAT3 is important for Tc17 polarization, both in vitro and in vivo. Adoptive transfer of highly purified, Ag-specific IL-17-secreting Tc17 cells into Ag-bearing hosts resulted in near complete conversion to an IFN-γ-secreting phenotype and substantial pulmonary pathology, demonstrating functional plasticity. Tc17 also accumulated to a greater extent than did Tc1 cells, suggesting that adoptive transfer of CD8 T cells cultured in Tc17 conditions may have therapeutic potential for diseases in which IFN-γ-producing cells are desired.

Purpose: To investigate the prognostic effect of the concentrations and clearance rates of plasma EBV DNA in metastatic/recurrent nasopharyngeal carcinoma (NPC).Experimental Design: Thirty relapsed and four previously nontreated metastatic NPC patients were treated according to the consensus guidelines of the head and neck cancer team in our hospital (i.v. chemotherapy first, followed by local irradiation boost and oral maintenance chemotherapy where applicable). Multiple plasma samples were collected during the first month of chemotherapy. Circulating EBV DNA concentrations were measured by a real-time quantitative PCR. The half-life values (t 1/2 ) of plasma EBV DNA clearance were calculated. The associations between clinical outcome and plasma EBV DNA assays were analyzed.Results: Tumor response evaluated after 12 weeks of treatment showed 14 complete responses (41.2%), 12 partial responses (35.3%), 7 stable diseases (20.6%), and 1 progression disease (2.9%). The plasma EBV DNA concentrations have no significant effects on outcome prediction. The t 1/2 of plasma EBV DNA clearance ranged from 1.85 to 28.29 days (median, 3.99). Patients with a short t 1/2 of plasma EBV DNA clearance have significantly higher complete response rate and overall survival than those with long t 1/2 . Multivariate analysis revealed a significant effect of the t 1/2 of plasma EBV DNA clearance on survival.Conclusions: The clearance rates of plasma EBV DNA during the first month of chemotherapy can predict tumor response and patient survival. Early change of chemotherapy regimen may be considered for patients with slow plasma EBV DNA clearance rate. Clin Cancer Res; 16(3); 1016-24. ©2010 AACR.Nasopharyngeal carcinoma (NPC) is distinct from other cancers of the head and neck by its epidemiology, histopathology, clinical characteristics, methods of treatment, and patterns of failure. Because of the inherent anatomic constraints and a high degree of radiosensitivity, radiotherapy has been the primary treatment for NPC patients without distant metastasis. Treatment failure in the past was due to a high rate of local recurrence and/or distant metastasis. However, advances in radiation oncology have improved the locoregional control, and treatment failure is now due mainly to distant metastasis. To date, the outcome of salvage treatment for relapse is still very poor, with the 5-year survival rates after local recurrence and distant metastasis being 9.4% to 30% and <5%, respectively (1-6). Because most metastatic/recurrent patients will succumb rapidly to the disease, the development of a quick and precise marker to predict treatment response is urgently needed.NPC has been proven as an EBV-associated cancer. EBV genome is present in the cells from almost every primary and metastatic NPC, regardless of the degree of tumor differentiation or the geographic origin of the patients. Recently, the quantification of plasma EBV DNA by the real-time quantitative PCR has been shown as a useful marker in the detection, monitoring, and prognos...