Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory.

PD-L1 on the surface of tumor cells binds its receptor PD-1 on effector T cells, thereby suppressing their activity. Antibody blockade of PD-L1 can activate an anti-tumor immune response leading to durable remissions in a subset of cancer patients. Here, we describe an alternative mechanism of PD-L1 activity involving its secretion in tumor-derived exosomes. Removal of exosomal PD-L1 inhibits tumor growth, even in models resistant to anti-PD-L1 antibodies. Exosomal PD-L1 from the tumor suppresses T cell activation in the draining lymph node. Systemically introduced exosomal PD-L1 rescues growth of tumors unable to secrete their own. Exposure to exosomal PD-L1-deficient tumor cells suppresses growth of wild-type tumor cells injected at a distant site, simultaneously or months later. Anti-PD-L1 antibodies work additively, not redundantly, with exosomal PD-L1 blockade to suppress tumor growth. Together, these findings show that exosomal PD-L1 represents an unexplored therapeutic target, which could overcome resistance to current antibody approaches

Different immune responses to three different vaccines following H6N1 low pathogenic avian influenza virus challenge in Taiwanese local chicken breeds.

BACKGROUND: H6N1 low pathogenic avian influenza virus (LPAIV) are frequently isolated in Taiwan and lead to significant economic losses, either directly or indirectly through association with other infectious diseases. This study investigates immune responses to three different vaccines following a H6N1 challenge in different local breeds. METHODS: Experimental animals were sampled from six local chicken breeds maintained at the National Chung-Hsing University, namely Hsin-Yi, Ju-Chi, Hua-Tung (Taiwan), Quemoy (Quemoy Island), Shek-Ki (China), Nagoya (Japan) and a specific pathogen free (SPF) White Leghorn line. A total number of 338 chickens have been distributed between a control and a challenge group, H6N1 challenge was performed at 7 weeks of age; vaccination against Newcastle Disease (ND), Infectious Bursal Disease (IBD) and Infectious Bronchitis (IB) was performed at 11 weeks. The anti-H6N1 LPAIV antibody titers were measured by ELISA at days 0, 7, 14 and 21 after challenge, and the anti-ND, anti-IBD and anti-IB antibody titers were measured by inhibition of hemagglutination test and ELISA at days 0, 14, 28 after vaccination. RESULTS: There was no effect of the H6N1 LPAIV challenge at 7 weeks of age on the subsequent responses to ND and IBD vaccine at 11 weeks of age, but, surprisingly, the H6N1 LPAIV challenge significantly affected antibody levels to IB vaccine in some breeds, since IB0 and IB14 antibody titers were lower in the challenge groups. However, there was no significant difference in IB28 antibody titers among the experimental groups. CONCLUSIONS: Local breeds have different immune response to H6N1 LPAIV challenge and subsequent vaccines. Differences dealt mainly with kinetics of response and with peak values. Quemoy exhibited higher antibody levels to H6N1, ND and IBD. The negative effect of the H6N1 LPAIV challenge on IB vaccine response may be related to the fact that both viruses target the lung tissues, and the type of local immune response induced by LPAIV challenge may not be favourable for birds to make optimum IB-specific antibody response.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Pyk2 activates the NLRP3 inflammasome by directly phosphorylating ASC and contributes to inflammasome-dependent peritonitis

The inflammasome adaptor protein, ASC, contributes to both innate immune responses and inflammatory diseases via self-oligomerization, which leads to the activation of the protease, caspase-1. Here, we report that the cytosolic tyrosine kinases, FAK and Pyk2, are differentially involved in NLRP3 and AIM2 inflammasome activation. The inhibition of FAK and Pyk2 with RNA interference or chemical inhibitors dramatically abolished ASC oligomerization, caspase-1 activation, and IL-1β secretion in response to NLRP3 or AIM2 stimulation. Pyk2 is phosphorylated by the kinase Syk and relocalizes to the ASC specks upon NLRP3 inflammasome activation. Pyk2, but not FAK, could directly phosphorylate ASC at Tyr146, and only the phosphorylated ASC could participate in speck formation and trigger IL-1β secretion. Moreover, the clinical-trial-tested Pyk2/FAK dual inhibitor PF-562271 reduced monosodium urate-mediated peritonitis, a disease model used for studying the consequences of NLRP3 activation. Our results suggest that although Pyk2 and FAK are involved in inflammasome activation, only Pyk2 directly phosphorylates ASC and brings ASC into an oligomerization-competent state by allowing Tyr146 phosphorylation to participate ASC speck formation and subsequent NLRP3 inflammation

Flexible Dye-Sensitized Solar Cell Based on Vertical ZnO Nanowire Arrays

Flexible dye-sensitized solar cells are fabricated using vertically aligned ZnO nanowire arrays that are transferred onto ITO-coated poly(ethylene terephthalate) substrates using a simple peel-off process. The solar cells demonstrate an energy conversion efficiency of 0.44% with good bending tolerance. This technique paves a new route for building large-scale cost-effective flexible photovoltaic and optoelectronic devices