抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMSs) with distinguishing features: CMS1 (microsatellite instability immune, 14%), hypermutated, microsatellite unstable and strong immune activation; CMS2 (canonical, 37%), epithelial, marked WNT and MYC signaling activation; CMS3 (metabolic, 13%), epithelial and evident metabolic dysregulation; and CMS4 (mesenchymal, 23%), prominent transforming growth factor-β activation, stromal invasion and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intratumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC-with clear biological interpretability-and the basis for future clinical stratification and subtype-based targeted interventions.

https://serval.unil.ch/resource/serval:BIB_6206DC2BFE0E.P001/REF.pdf

The consensus molecular subtypes of colorectal cancer

https://escholarship.org/content/qt5st231s3/qt5st231s3.pdf?t=omsseb

Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy.

We present the science and technology roadmap for graphene, related two-dimensional crystals, and hybrid systems, targeting an evolution in technology, that might lead to impacts and benefits reaching into most areas of society. This roadmap was developed within the framework of the European Graphene Flagship and outlines the main targets and research areas as best understood at the start of this ambitious project. We provide an overview of the key aspects of graphene and related materials (GRMs), ranging from fundamental research challenges to a variety of applications in a large number of sectors, highlighting the steps necessary to take GRMs from a state of raw potential to a point where they might revolutionize multiple industries. We also define an extensive list of acronyms in an effort to standardize the nomenclature in this emerging field.

/pdf/science-and-technology-roadmap-for-graphene-related-two-4q9m7czlkc.pdf

Science and technology roadmap for graphene, related two-dimensional crystals, and hybrid systems

Macrophages are crucial drivers of tumour-promoting inflammation. Tumour-associated macrophages (TAMs) contribute to tumour progression at different levels: by promoting genetic instability, nurturing cancer stem cells, supporting metastasis, and taming protective adaptive immunity. TAMs can exert a dual, yin-yang influence on the effectiveness of cytoreductive therapies (chemotherapy and radiotherapy), either antagonizing the antitumour activity of these treatments by orchestrating a tumour-promoting, tissue-repair response or, instead, enhancing the overall antineoplastic effect. TAMs express molecular triggers of checkpoint proteins that regulate T-cell activation, and are targets of certain checkpoint-blockade immunotherapies. Other macrophage-centred approaches to anticancer therapy are under investigation, and include: inhibition of macrophage recruitment to, and/or survival in, tumours; functional re-education of TAMs to an antitumour, 'M1-like' mode; and tumour-targeting monoclonal antibodies that elicit macrophage-mediated extracellular killing, or phagocytosis and intracellular destruction of cancer cells. The evidence supporting these strategies is reviewed herein. We surmise that TAMs can provide tools to tailor the use of cytoreductive therapies and immunotherapy in a personalized medicine approach, and that TAM-focused therapeutic strategies have the potential to complement and synergize with both chemotherapy and immunotherapy.

/pdf/tumour-associated-macrophages-as-treatment-targets-in-3gdbul5s9u.pdf

Tumour-associated macrophages as treatment targets in oncology

Spin currents can apply useful torques in spintronic devices. The spin Hall effect has been proposed as a source of spin current, but its modest strength has limited its usefulness. We report a giant spin Hall effect (SHE) in β-tantalum that generates spin currents intense enough to induce efficient spin-torque switching of ferromagnets at room temperature. We quantify this SHE by three independent methods and demonstrate spin-torque switching of both out-of-plane and in-plane magnetized layers. We furthermore implement a three-terminal device that uses current passing through a tantalum-ferromagnet bilayer to switch a nanomagnet, with a magnetic tunnel junction for read-out. This simple, reliable, and efficient design may eliminate the main obstacles to the development of magnetic memory and nonvolatile spin logic technologies.

Spin-torque switching with the giant spin hall effect of tantalum

We report a giant spin Hall effect in β-W thin films. Using spin torque induced ferromagnetic resonance with a β-W/CoFeB bilayer microstrip, we determine the spin Hall angle to be |θSHβ-W|=0.30±0.02, large enough for an in-plane current to efficiently reverse the orientation of an in-plane magnetized CoFeB free layer of a nanoscale magnetic tunnel junction adjacent to a thin β-W layer. From switching data obtained with such 3-terminal devices, we independently determine |θSHβ-W|=0.33±0.06. We also report variation of the spin Hall switching efficiency with W layers of different resistivities and hence of variable (α and β) phase composition.

Spin transfer torque devices utilizing the giant spin Hall effect of tungsten

The MYC oncogene codes for a transcription factor that is overexpressed in many human cancers. Here we show that MYC regulates the expression of two immune checkpoint proteins on the tumor cell surface: the innate immune regulator CD47 (cluster of differentiation 47) and the adaptive immune checkpoint PD-L1 (programmed death-ligand 1). Suppression of MYC in mouse tumors and human tumor cells caused a reduction in the levels of CD47 and PD-L1 messenger RNA and protein. MYC was found to bind directly to the promoters of the Cd47 and Pd-l1 genes. MYC inactivation in mouse tumors down-regulated CD47 and PD-L1 expression and enhanced the antitumor immune response. In contrast, when MYC was inactivated in tumors with enforced expression of CD47 or PD-L1, the immune response was suppressed, and tumors continued to grow. Thus, MYC appears to initiate and maintain tumorigenesis, in part, through the modulation of immune regulatory molecules.

http://science.sciencemag.org/content/sci/early/2016/03/09/science.aac9935.full.pdf

MYC regulates the antitumor immune response through CD47 and PD-L1

We report a giant spin Hall effect (SHE) in {\beta}-W thin films. Using spin torque induced ferromagnetic resonance with a {\beta}-W/CoFeB bilayer microstrip we determine the spin Hall angle to be |\theta|=0.30\pm0.02, large enough for an in-plane current to efficiently reverse the orientation of an in-plane magnetized CoFeB free layer of a nanoscale magnetic tunnel junction adjacent to a thin {\beta}-W layer. From switching data obtained with such 3-terminal devices we independently determine |\theta|=0.33\pm0.06. We also report variation of the spin Hall switching efficiency with W layers of different resistivities and hence of variable ({\alpha} and {\beta}) phase composition.

The MYC proto-oncogene has been implicated in the pathogenesis of most types of human tumors. MYC activation alone in many normal cells is restrained from causing tumorigenesis through multiple genetic and epigenetically controlled checkpoint mechanisms, including proliferative arrest, apoptosis, and cellular senescence. When pathologically activated in a permissive epigenetic and/or genetic context, MYC bypasses these mechanisms, enforcing many of the "hallmark" features of cancer, including relentless tumor growth associated with DNA replication and transcription, cellular proliferation and growth, protein synthesis, and altered cellular metabolism. MYC mandates tumor cell fate, by inducing stemness and blocking cellular senescence and differentiation. Additionally, MYC orchestrates changes in the tumor microenvironment, including the activation of angiogenesis and suppression of the host immune response. Provocatively, brief or even partial suppression of MYC back to its physiological levels of activation can result in the restoration of intrinsic checkpoint mechanisms, resulting in acute and sustained tumor regression, associated with tumor cells undergoing proliferative arrest, differentiation, senescence, and apoptosis, as well as remodeling of the tumor microenvironment, recruitment of an immune response, and shutdown of angiogenesis. Hence, tumors appear to be "addicted" to MYC because of both tumor cell-intrinsic, cell-autonomous and host-dependent, immune cell-dependent mechanisms. Both the trajectory and persistence of many human cancers require sustained MYC activation. Multiscale mathematical modeling may be useful to predict when tumors will be addicted to MYC. MYC is a hallmark molecular feature of both the initiation and maintenance of tumorigenesis.

http://perspectivesinmedicine.cshlp.org/content/4/6/a014241.full.pdf

Yulin Li

Papers

Spin-torque switching with the giant spin hall effect of tantalum

Spin transfer torque devices utilizing the giant spin Hall effect of tungsten

MYC regulates the antitumor immune response through CD47 and PD-L1

Spin transfer torque devices utilizing the giant spin Hall effect of tungsten

MYC Activation Is a Hallmark of Cancer Initiation and Maintenance