An Immune Signature for Risk Stratification and Therapeutic Prediction in Helicobacter pylori-Infected Gastric Cancer

Helicobacter pylori (HP) infection is the greatest risk factor for gastric cancer (GC). Increasing evidence has clarified that tumor immune microenvironment (TIME) is closely related to the prognosis and therapeutic efficacy of HP-positive (HP+) GC patients. In this study, we aimed to construct a novel immune-related signature for predicting the prognosis and immunotherapy efficacy of HP+ GC patients. A total of 153 HP+ GC from three different cohorts were included in this study. An Immune-Related prognostic Signature for HP+ GC patients (IRSHG) was established using Univariate Cox regression, the LASSO algorithm, and Multivariate Cox regression. Univariate and Multivariate analyses proved IRSHG was an independent prognostic predictor for HP+ GC patients, and an IRSHG-integrated nomogram was established to quantitatively assessthe prognostic risk. The low-IRSHG group exhibited higher copy number load and distinct mutation profiles compared with the high-IRSHG group. In addition, the difference of hallmark pathways and immune cells infiltration between the two groups was investigated. Notably, tumor immune dysfunction and exclusion (TIDE) analysis indicated that the low-IRSHG group had a higher sensitivity to anti-PD-1 immunotherapy, which was validated by an external pabolizumab treatment cohort. Moreover, 98 chemotherapeutic drugs and corresponding potential biomarkers were identified for two groups, and several drugs with potential ability to reverse IRSHG score were identified using CMap analysis. Collectively, IRSHG may serve as a promising biomarker for survival outcome as well as immunotherapy efficacy. Furthermore, it can also help to prioritize potential therapeutics for HP+ GC patients, providing new insight for the personalized treatment of HP-infected GC

CD177 drives the transendothelial migration of Treg cells enriched in human colorectal cancer

Abstract Objectives Regulatory T (Treg) cells regulate immunity in autoimmune diseases and cancers. However, immunotherapies that target tumor‐infiltrating Treg cells often induce unwanted immune responses and tissue inflammation. Our research focussed on exploring the expression pattern of CD177 in tumor‐infiltrating Treg cells with the aim of identifying a potential target that can enhance immunotherapy effectiveness. Methods Single‐cell RNA sequencing (scRNA‐seq) data and survival data were obtained from public databases. Twenty‐one colorectal cancer patient samples, including fresh tumor tissues, peritumoral tissues and peripheral blood mononuclear cells (PBMCs), were analysed using flow cytometry. The transendothelial activity of CD177+ Treg cells was substantiated using in vitro experiments. Results ScRNA‐seq and flow cytometry results indicated that CD177 was exclusively expressed in intratumoral Treg cells. CD177+ Treg cells exhibited greater activation status and expressed elevated Treg cell canonical markers and immune checkpoint molecules than CD177− Treg cells. We further discovered that both intratumoral CD177+ Treg cells and CD177‐overexpressing induced Treg (iTreg) cells had lower levels of PD‐1 than their CD177− counterparts. Moreover, CD177 overexpression significantly enhanced the transendothelial migration of Treg cells in vitro. Conclusions These results demonstrated that Treg cells with higher CD177 levels exhibited an enhanced activation status and transendothelial migration capacity. Our findings suggest that CD177 may serve as an immunotherapeutic target and that overexpression of CD177 may improve the efficacy of chimeric antigen receptor T (CAR‐T) cell therapy

Tuning Electrochemical Properties of Li-Rich Layered Oxide Cathodes by Adjusting Co/Ni Ratios and Mechanism Investigation Using in situ X‑ray Diffraction and Online Continuous Flow Differential Electrochemical Mass Spectrometry

Owing to high specific capacity of ∼250 mA h g^–1, lithium-rich layered oxide cathode materials (Li_1+<i>x</i>Ni_<i>y</i>Co_<i>z</i>Mn_{(3–<i>x</i>–2<i>y</i>–3<i>z</i>)/4}O₂) have been considered as one of the most promising candidates for the next-generation cathode materials of lithium ion batteries. However, the commercialization of this kind of cathode materials seriously restricted by voltage decay upon cycling though Li-rich materials with high cobalt content have been widely studied and show good capacity. This research successfully suppresses voltage decay upon cycling while maintaining high specific capacity with low Co/Ni ratio in Li-rich cathode materials. Online continuous flow differential electrochemical mass spectrometry (OEMS) and in situ X-ray diffraction (XRD) techniques have been applied to investigate the structure transformation of Li-rich layered oxide materials during charge–discharge process. The results of OEMS revealed that low Co/Ni ratio lithium-rich layered oxide cathode materials released no lattice oxygen at the first charge process, which will lead to the suppression of the voltage decay upon cycling. The in situ XRD results displayed the structure transition of lithium-rich layered oxide cathode materials during the charge–discharge process. The Li_1.13Ni_0.275Mn_0.580O₂ cathode material exhibited a high initial medium discharge voltage of 3.710 and a 3.586 V medium discharge voltage with the lower voltage decay of 0.124 V after 100 cycles