The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer

Programmed death 1 (PD-1) is a co-inhibitory receptor in the CD28/CTL-4 family, and functions as a negative regulator of the immune system. Tumor-infiltrating lymphocytes (TIL) in many epithelial cancers express PD-1, suggesting that antitumor immunity may be modulated by the PD-1/PD-L1 signaling pathway, and promising results from two recent clinical trials with monoclonal antibodies targeting PD-1 or PD-L1 confirm the clinical relevance of this pathway in human cancer. To explore the role of PD-1+ TIL in human breast cancer, we performed immunohistochemistry studies on a tissue microarray encompassing 660 breast cancer cases with detailed clinical annotation and outcomes data. PD-1+ TIL were present in 104 (15.8%) of the 660 breast cancer cases. Their presence was associated with tumor size, grade, and lymph node status, and was differentially associated with the intrinsic subtypes of breast cancer. In univariate survival analyses, the presence of PD-1+ TIL was associated with a significantly worse overall survival (HR=2.736, p<0.001). In subset analyses, the presence of PD-1+ TIL was associated with significantly worse overall survival in the luminal B HER2− subtype (HR=2.678, p<0.001), the luminal B HER2+ subtype (HR=3.689, p<0.001), and the basal-like subtype (HR=3.140, p<0.001). This is the first study to demonstrate that the presence of PD-1+ TIL is associated with poor prognosis in human breast cancer, with important implications for the potential application of antibody therapies targeting the PD-1/PD-L1 signaling pathway in this diseas

PTP1B expression is an independent positive prognostic factor in human breast cancer

Protein tyrosine phosphatase 1B (PTP1B) is a non-transmembrane protein tyrosine phosphatase that has come into focus as a critical regulator of multiple signaling pathways. The role of PTP1B in breast cancer remains unclear with evidence suggesting that PTP1B can exert both tumor-suppressing and tumor-promoting effects. To better define the role of PTP1B in human breast cancer, and its relationship with HER2, we performed immunohistochemical studies on a large cohort of functionally annotated primary breast cancer specimens. 683 of 1,402 (49%) evaluable primary breast cancers are positive for PTP1B. There is no statistically significant association between PTP1B expression and age, tumor size, T stage, histologic grade, lymph node status, or histological subtype. Of note, there is no significant association between PTP1B expression and HER2 expression (PTP1B expression53.1% in HER2+ cancers vs. 47.5% in HER2− cancers, p=0.0985). However, PTP1B expression is significantly associated with estrogen receptor expression (PTP1B expression50.7% in ER+ cancers vs. 43.1% in ER− cancers, p=0.0137) and intrinsic molecular subtype (PTP1B expression53.9% in the luminal B HER2+ subtype and 37.9% in the basal-like subtype). Of note, multivariate analyses demonstrate that PTP1B is an independent predictor of improved survival in breast cancer (HR 0.779, p=0.006). Taken together, we demonstrate in the largest study to date that (1) PTP1B is commonly expressed in breast cancer, (2) there is no association or functional impact of PTP1B expression in HER2+ breast cancer, and (3) PTP1B expression in breast cancer is associated with significantly improved clinical outcome. Until additional studies are performed, caution should be exercised in using PTP1B inhibitors in human breast cance

A low-cost, portable optical explosive-vapour sensor

This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under agreement no 284747. IDWS acknowledges a Royal Society Wolfson Research Merit Award. Data supporting this research can be found at http://dx.doi.org/10.17630/5868c89a-7019-4897-9c54-24ccc551a6e6.Humanitarian demining requires a broad range of methodologies and instrumentation for reliable identification of landmines, antipersonnel mines, and other explosive remnants of war (ERWs). Optical sensing methods are ideal for this purpose due to advantages in sensitivity, time-of-response and small form factor. In this work we present a portable photoluminescence-based sensor for nitroaromatic vapours based on the conjugated polymer Super Yellow integrated into an instrument comprising an excitation LED, photodiode, Arduino microprocessor and pumping mechanics for vapour delivery. The instrument was shown to be sensitive to few-ppb concentrations of explosive vapours under laboratory conditions, and responds to simulated buried landmine vapour. The results indicate that a lightweight, easy-to-operate, lowcost and highly-sensitive optical sensor can be readily constructed for landmine and ERW detection in the field, with potential to aid worldwide efforts in landmine mitigation.PostprintPeer reviewe

Ormosil-coated conjugated polymers for the detection of explosives in aqueous environments

This project has received funding from the TIRAMISU project, funded by the European Commission’s Seventh Framework Programme (FP7/2007-2013) under grant agreement 284747, and the Engineering and Physical Sciences Research Council under grants EP/K503940/1, EP/K503162/1, EP/N509759/1. IDWS acknowledges a Royal Society Wolfson Research Merit Award. The research data supporting this publication can be accessed at http://dx.doi.org/10.17630/3875a099-bb75-4ae1-82e5-0b98b6b7ebc6.A fluorescence-based sensor for detecting explosives, based on a conjugated polymer coated with an ormosil layer, has been developed for use in aqueous environments. The conjugated polymer Super Yellow was spin-coated onto glass substrates prior to a further spin-coating of an MTEOS/TFP-TMOS-based ormosil film, giving an inexpensive, solution-based barrier material for ruggedization of the polymer to an aqueous environment. The sensors showed good sensitivity to 2,4-DNT in the aqueous phase at micromolar and millimolar concentrations, and also showed good recovery of fluorescence when the explosive was removed.PostprintPeer reviewe

The Energy Spectrum of TeV Gamma-Rays from the Crab Nebula as measured by the HEGRA system of imaging air Cherenkov telescopes

The Crab Nebula has been observed by the HEGRA (High-Energy Gamma-Ray Astronomy) stereoscopic system of imaging air Cherenkov telescopes (IACTs) for a total of about 200 hrs during two observational campaigns: from September 1997 to March 1998 and from August 1998 to April 1999. The recent detailed studies of system performance give an energy threshold and an energy resolution for gamma-rays of 500 GeV and ~ 18%, respectively. The Crab energy spectrum was measured with the HEGRA IACT system in a very broad energy range up to 20 TeV, using observations at zenith angles up to 65 degrees. The Crab data can be fitted in the energy range from 1 to 20 TeV by a simple power-law, which yields dJg/dE = (2.79+/-0.02 +/- 0.5) 10^{-7} E^{-2.59 +/- 0.03 +/- 0.05}, ph m^{-2} s^{-1} TeV^{-1} The Crab Nebula energy spectrum, as measured with the HEGRA IACT system, agrees within 15% in the absolute scale and within 0.1 units in the power law index with the latest measurements by the Whipple, CANGAROO and CAT groups, consistent within the statistical and systematic errors quoted by the experiments. The pure power-law spectrum of TeV gamma-rays from the Crab Nebula constrains the physics parameters of the nebula environment as well as the models of photon emission.Comment: to appear in ApJ, 29 pages, 6 figure