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Chimeric antigen receptor (CAR) T-cell immunotherapy refers to an adoptive immunotherapy that has rapidly developed in recent years. It is a novel type of treatment that enables T cells to express specific CARs on their surface, then returns these T cells to tumor patients to kill the corresponding tumor cells. Significant strides in CAR-T cell immunotherapy against hematologic malignancies have elicited research interest among scholars in the treatment of solid tumors. Nonetheless, in contrast with the efficacy of CAR-T cell immunotherapy in the treatment of hematologic malignancies, its general efficacy against solid tumors is insignificant. This has been attributed to the complex biological characteristics of solid tumors. CAR-T cells play a better role in solid tumors, for instance by addressing obstacles including the lack of specific targets, inhibition of tumor microenvironment (TME), homing barriers of CAR-T cells, differentiation and depletion of CAR-T cells, inhibition of immune checkpoints, trogocytosis of CAR-T cells, tumor antigen heterogeneity, etc. This paper reviews the obstacles influencing the efficacy of CAR-T cell immunotherapy in solid tumors, their mechanism, and coping strategies, as well as economic restriction of CAR-T cell immunotherapy and its solutions. It aims to provide some references for researchers to better overcome the obstacles that affect the efficacy of CAR-T cells in solid tumors.

A bibliometric and knowledge-map analysis is used to explore hotspots' evolution and development trends in the CAR-T cell field. By looking for research hotspots and new topics, we can provide new clues and ideas for researchers in this field. The articles and reviews regarding CAR-T cells were retrieved and obtained from the Web of Science Core Collection (WOSCC) on October 28th, 2021. CtieSpace [version 5.8.R3 (64-bit)] and VOSviewer (version 1.6.17) were used to conduct the bibliometric and knowledge-map analysis. 660 authors from 488 institutions in 104 countries/regions published 6,867 papers in 1,212 academic journals. The United States was absolutely in the leading position in this research field. The institution that contributed the most publications was the University of Pennsylvania. Carl H June published the most articles, while Shannon L Maude had the most co-citations. However, there was little cooperation between countries. After 2012, cooperation among various institutions was also small. The journals that published the most CAR-T cell-related papers were and . Nevertheless, and were the most commonly co-cited journals. The most influential research hotspots were the research of CAR-T cells in hematological malignancies, the related research of cytokine release syndrome (CRS), CD19, and the anti-tumor activity and efficacy of CAR-T cells. The latest hotspots and topics included the study of CAR-T cells in solid tumors, universal CAR-T cells, CAR-NK cells, CD22, and anakinra (the IL-1 receptor antagonist). The research of CAR-T cells in solid tumors was a rapidly developing hot field. Emerging topics in this field mainly included the study of CAR-T cells in glioblastoma (related targets: IL13Rα2, EGFRvIII, and HER2), neuroblastoma (related target: GD2), sarcoma (related target: HER2), and pancreatic cancer (related target: mesothelin), especially glioblastoma. As an anti-tumor therapy with great potential and clinical application prospects, CAR-T cell therapy is still in a stage of rapid development. The related field of CAR-T cells will remain a research hotspot in the future.

In recent years, chimeric antigen receptor T cells (CAR-T cells) have been faced with the problems of weak proliferation and poor persistence in the treatment of some malignancies. Researchers have been trying to perfect the function of CAR-T by genetically modifying its structure. In addition to the participation of T cell receptor (TCR) and costimulatory signals, immune cytokines also exert a decisive role in the activation and proliferation of T cells. Therefore, genetic engineering strategies were used to generate cytokines to enhance tumor killing function of CAR-T cells. When CAR-T cells are in contact with target tumor tissue, the proliferation ability and persistence of T cells can be improved by structurally or inductively releasing immunoregulatory molecules to the tumor region. There are a large number of CAR-T cells studies on gene-edited cytokines, and the most common cytokines involved are interleukins (IL-7, IL-12, IL-15, IL-18, IL-21, IL-23). Methods for the construction of gene-edited interleukin CAR-T cells include co-expression of single interleukin, two interleukin, interleukin combined with other cytokines, interleukin receptors, interleukin subunits, and fusion inverted cytokine receptors (ICR). Preclinical and clinical trials have yielded positive results, and many more are under way. By reading a large number of literatures, we summarized the functional characteristics of some members of the interleukin family related to tumor immunotherapy, and described the research status of gene-edited interleukin CAR-T cells in the treatment of malignant tumors. The objective is to explore the optimized strategy of gene edited interleukin-CAR-T cell function.

Pancreatic cancer ranks among the most lethal digestive malignancies, exhibiting a steadily increasing incidence and mortality worldwide. Despite significant advances in cancer research, the 5-year survival rate remains below 10%, predominantly due to delayed diagnosis and limited therapeutic options. Concurrently, the gut microbiota—an integral component of host physiology—has emerged as a crucial player in the pathogenesis of pancreatic cancer. Mounting evidence indicates that alterations in gut microbial composition and function may influence tumor initiation, progression, and response to therapy. This review provides an in-depth examination of the intricate interplay between the gut microbiome and pancreatic cancer, highlighting potential diagnostic biomarkers and exploring microbiome-targeted therapeutic strategies to improve patient outcomes. Plain language summary How gut bacteria may affect pancreatic cancer and help improve treatment Pancreatic cancer is a deadly disease with few early symptoms and limited treatment options. Recent research suggests that the bacteria living in our gut, known as gut microbiota, may play a role in the development and treatment of pancreatic cancer. This review looks at how changes in gut microbiota could influence the onset and progression of pancreatic cancer. We also explore new possibilities for using gut bacteria to help diagnose pancreatic cancer earlier and develop better treatment options. Understanding the relationship between gut microbiota and pancreatic cancer could lead to new strategies to improve patient outcomes and increase survival rates.

Background Hepatocellular carcinoma (HCC) is frequently identified at advanced stages. This constrains therapeutic options and results in poor prognosis. P2RX4 is an ATP-gated ion channel that modulates calcium influx. It participates in cellular proliferation, inflammatory processes, and immunological reactions. Nonetheless, its role in HCC remains poorly comprehended. This study explored the expression, function, and immunological effects of P2RX4 in HCC. Methods We examined P2RX4 expression using TCGA-LIHC and TIMER2.0 databases. Protein levels were validated using immunohistochemistry in 140 HCC tissues. A prognostic model was developed utilising P2RX4 expression. In vitro investigations were conducted subsequent to the silencing of P2RX4. The experiments encompassed cell proliferation, invasion, and colony formation. We further conducted transcriptome sequencing. Ion concentrations were quantified with ICP-OES. PI3K/AKT activation was evaluated using Western blotting. Results P2RX4 exhibited elevated expression in HCC tissues. Its expression was associated with advanced tumor stage and poor prognosis. Silencing of P2RX4 decreased tumour cell proliferation and invasion. It also reduced intracellular calcium levels and inhibited AKT phosphorylation. Elevated P2RX4 levels correlated with an increased presence of M0 macrophages and Tregs, a reduced number of monocytes, and a poorer anticipated response to immunotherapy. Conclusions P2RX4 may facilitate HCC progression by augmenting calcium influx, activating the PI3K/AKT pathway, and diminishing anti-tumor immunity. It may function as a biomarker and therapeutic target in HCC. Additional, in vivo investigations are required to validate these findings.

Background Over the past few decades, the global incidence of cholangiocarcinoma has risen overall. In particular, the incidence of intrahepatic cholangiocarcinoma increased by 109% over a ten-year period, rising from 0.67 per 100,000 in 2007 to 1.40 per 100,000 in 2016 1 . Epidemiological studies have suggested that cholecystitis may increase the risk of hepatobiliary cancers. However, whether this association indicates an independent causal relationship remains unclear. Given that observational studies are prone to residual confounding and bias, limiting the strength of causal inference. Our study aimed to evaluate whether cholecystitis is an independent risk factor for cholangiocarcinoma. Methods Instrumental variables were identified as independent single nucleotide polymorphisms highly associated with cholecystitis ( n  = 25). The entire dataset from the Integrative Epidemiology Unit (IEU) publicly available genome-wide association studies (GWAS) was utilized to obtain cholangiocarcinoma outcome data ( n  = 25). In this study, five MR statistical techniques (Inverse Variance Weighted, MR Egger, Weighted Median, Simple Mode, and Weighted mode) were used. The MR Egger intercept test, leave-one-out analysis, and the funnel plot were all utilized in sensitivity analyses. Results Results of the Inverse Variance Weighted (IVW) method genetically predicted cholecystitis was associated with higher risk of cholangiocarcinoma, with an odds ratio of 2.915 (95% CI = 1.122–7.575, P  = 0.038). Weighted Median Method also demonstrated consistent direction of effect ( P  = 0.016). However, MR-Egger, Simple Mode, and Weighted Mode all showed no statistical significance ( P > 0.05). Both funnel plots and MR Egger intercepts indicated the absence of any directional pleiotropic effects between cholecystitis and cholangiocarcinoma. Conclusion We found evidence supporting a causal effect between cholecystitis and cholangiocarcinoma, indicating an increased likelihood of cholangiocarcinoma in patients with cholecystitis through MR analysis.These findings may help inform clinical strategies for the management of cholecystitis, with the aim of potentially reducing the risk of cholangiocarcinoma.

Objective To investigate the prognostic significance and immunological implication of transmembrane protein 119 (TMEM119) in stomach adenocarcinoma (STAD). Methods This study included STAD-associated data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. In addition, TMEM119 expression levels were analysed by immunohistochemistry in tissue samples from patients with STAD (with microsatellite instability or microsatellite stability). Gene Set Enrichment Analysis (GSEA) was conducted to explore signalling pathways related to TMEM119 in STAD. Additionally, CIBERSORT and ESTIMATE algorithms were applied to examine the relationship between TMEM119 expression and tumour-infiltrating immune cells, as well as the tumour microenvironment. Results Surgical specimens from 100 patients with STAD (50 each with microsatellite stability or microsatellite instability); TCGA RNA-sequence and clinical data from 375 STAD tumour tissues and 32 paracancerous tissues; and two GEO datasets (GSE27342, comprising 80 paracancerous tissues and 80 tumour tissues; and GSE84437, comprising 433 tumour samples) were analysed. TMEM119 was found to be elevated in STAD, and associated with poor prognosis. Clinical gastric cancer tissues exhibited increased TMEM119 expression. TMEM119 was enriched in immune-related functions and pathways. TMEM119 correlated with immune checkpoint genes, tumour mutational burden, and microsatellite instability. TMEM119 was positively correlated with tumour-infiltrating immune cells, tumour microenvironment, mannose receptor C-type I (CD206), and programmed cell death-ligand 1 (PD-L1), while inversely related to nitric oxide synthase 2. Conclusions TMEM119 may be a potential immune-related biomarker for STAD prognosis and therapeutic targeting.

Background Disulfidptosis, a newly discovered form of cell death resulting from disulfide stress, remains unclear in its role in stomach adenocarcinoma (STAD). This study aimed to establish a novel disulfidptosis and cuproptosis-related lncRNAs (DCRLs) signature for STAD. Methods We sourced RNA-seq data for STAD from the The Cancer Genome Atlas (TCGA) repository. STAD samples underwent nonnegative matrix factorization (NMF) clustering to identify distinct molecular subgroups, followed by Lasso-Cox regression to construct a prognostic model for DCRLs. Subsequently, the model’s clinical predictive capacity was evaluated using a nomogram. The expression of risk lncRNAs was validated via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results The samples were classified into three molecular subtypes based on DCRLs, with the C1 subtype demonstrating the worst prognosis. We identified four independent prognostic lncRNAs (AC016394.2, NUTM2A-AS1, OIP5-AS1, and LIMS1-AS1) and constructed a prognostic risk model. Survival analysis revealed that high-risk patients had a poorer prognosis. The model’s risk score was strongly correlated with the tumor mutational burden (TMB), microsatellite instability (MSI), immune subtypes, and tumor-infiltrating immune cells (TIICs) in the tumor microenvironment (TME). Analysis utilizing the Tumor Immune Dysfunction and Exclusion (TIDE) revealed a higher risk of tumor immune evasion among high-risk patients. Moreover, the expression levels of four risk lncRNAs were higher in the majority of gastric cancer cell lines compared to normal cell lines. Conclusion Our study establishes a risk model that effectively predicts clinical outcomes and immune response in STAD.

Background Chronic coronary syndrome (CCS) is a major public health burden; its pathogenesis involves atherosclerosis and endothelial dysfunction. Endothelin-1 (ET-1) and nitric oxide (NO) are vasoactive substances synthesized by endothelial cells that play a crucial role in CCS development. The Gensini score (GS) is used for evaluating CCS severity based on lumen segment changes, stenosis degree, and coronary stenosis site. Methods This prospective study included 71 patients with CCS; we evaluated the relationships between GS and ET-1 and NO serum levels were evaluated in these patients. The GS was calculated for all patients. Serum ET-1 & NO levels among other laboratory parameters were measured. Results The high GS group had higher ET-1 and relatively NO expressions in the than the low GS group. GS was positively correlated with ET-1 and negatively correlated with NO, T4, and TSH levels. The results of the multiple linear regression analysis showed that ET-1 had the most significant effect on GS. Conclusions We found a strong association between ET-1, NO, and CCS severity. A combination of ET-1, NO, and GS is an essential predictor of CCS disease severity.

Boron neutron capture therapy (BNCT) is a two-step targeted radiotherapy technique, which selectively delivers 10 B atoms to tumor tissues, leading to selective tumor destruction through thermal neutron irradiation. BNCT, which utilizes boron agents, such as BPA and BSH, has demonstrated promising results in tumor treatment. However, it still faces several challenges, including insufficient tumor targeting, rapid in vivo metabolism, and high doses due to poor solubility. To address these challenges, nanotechnology-based boron drug delivery systems have emerged as a crucial strategy to enhance the therapeutic efficacy of BNCT. This paper thus summarizes the respective drug-carrying modes and provides an evaluation of the advantages and disadvantages of inorganic nanomaterials (e.g., gold nanoparticles, boron nanoparticles, carbon nanoparticles, silica nanoparticles, magnetic nanoparticles), organic nanomaterials (e.g., liposomes, polymer nanoparticles, dendritic macromolecules, micelles), and natural nanomaterials. In addition, we discuss pressing issues and future research directions regarding the use of nanomaterials as boron drug carriers, with the aim of offering valuable insights into the advancement of these materials in both basic and clinical research application.