Strategies to reinvigorate exhausted CD8+ T cells in tumor microenvironment

CD8+ T cell exhaustion is a stable dysfunctional state driven by chronic antigen stimulation in the tumor microenvironment (TME). Differentiation of exhausted CD8+ T cells (CD8+ TEXs) is accompanied by extensive transcriptional, epigenetic and metabolic reprogramming. CD8+ TEXs are mainly characterized by impaired proliferative and cytotoxic capacity as well as the increased expression of multiple co-inhibitory receptors. Preclinical tumor studies and clinical cohorts have demonstrated that T cell exhaustion is firmly associated with poor clinical outcomes in a variety of cancers. More importantly, CD8+ TEXs are regarded as the main responder to immune checkpoint blockade (ICB). However, to date, a large number of cancer patients have failed to achieve durable responses after ICB. Therefore, improving CD8+ TEXs may be a breakthrough point to reverse the current dilemma of cancer immunotherapy and eliminate cancers. Strategies to reinvigorate CD8+ TEXs in TME mainly include ICB, transcription factor-based therapy, epigenetic therapy, metabolism-based therapy and cytokine therapy, which target on different aspects of exhaustion progression. Each of them has its advantages and application scope. In this review, we mainly focus on the major advances of current strategies to reinvigorate CD8+ TEXs in TME. We summarize their efficacy and mechanisms, identify the promising monotherapy and combined therapy and propose suggestions to enhance the treatment efficacy to significantly boost anti-tumor immunity and achieve better clinical outcomes

Hidden phase in a two-dimensional Sn layer stabilized by modulation hole doping

Semiconductor surfaces and ultrathin interfaces exhibit an interesting variety of two-dimensional quantum matter phases, such as charge density waves, spin density waves and superconducting condensates. Yet, the electronic properties of these broken symmetry phases are extremely difficult to control due to the inherent difficulty of doping a strictly two-dimensional material without introducing chemical disorder. Here we successfully exploit a modulation doping scheme to uncover, in conjunction with a scanning tunnelling microscope tip-assist, a hidden equilibrium phase in a hole-doped bilayer of Sn on Si(111). This new phase is intrinsically phase separated into insulating domains with polar and nonpolar symmetries. Its formation involves a spontaneous symmetry breaking process that appears to be electronically driven, notwithstanding the lack of metallicity in this system. This modulation doping approach allows access to novel phases of matter, promising new avenues for exploring competing quantum matter phases on a silicon platform

Two-Dimensional Platinum Telluride with Ordered Te Vacancy Superlattice for Efficient and Robust Hydrogen Evolution

Defect engineering to activate the basal planes of transition metal dichalcogenides (TMDs) is critical for the development of TMD-based electrocatalysts as the chemical inertness of basal planes restrict their potential applications in hydrogen evolution reaction (HER). Here, we report the synthesis and evaluation of few-layer (7x7)-PtTe2-x with an ordered, well-defined and high-density Te vacancy superlattice. Compared with pristine PtTe2, (2x2)-PtTe2-x and Pt(111), (7x7)-PtTe2-x exhibits superior HER activities in both acidic and alkaline electrolytes due to its rich structures of undercoordinated Pt sites. Furthermore, the (7x7)-PtTe2-x sample features outstanding catalytic stability even compared to the state-of-the-art Pt/C catalyst. Theoretical calculations reveal that the interactions between various undercoordinated Pt sites due to proximity effect can provide superior undercoordinated Pt sites for hydrogen adsorption and water dissociation. This work will enrich the understanding of the relationship between defect structures and electrocatalytic activities and provide a promising route to develop efficient Pt-based TMD electrocatalysts

Effect of Substrate Doping Concentration on Quantum Well States of Pb Island Grown on Si(111)

The interaction between the metallic film/island and the semiconductor substrate is important to the electronic properties of metallic nanostructure grown on semiconductor substrate. Here, we report a series of comparison experiments to investigate the effect of doping concentration of Si substrates on the quantum well state (QWS). Using scanning tunneling microscopy, we observed that the apparent QWS energy positions show a strong dependence on the substrate used and on the sample temperature. Further experimental results by varying the height of scanning tunneling microscope tip over the Pb island uncovered that the observed apparent QWS energy position changes mainly come from the partial bias voltage drop on the combined resistance of the Pb wetting layer and the substrate, which is comparable with the vacuum tunneling resistance at low temperatures. (C) 2009 Elsevier B.V. All rights reserved