Esophageal squamous cell carcinoma is the main histological type of esophageal cancer in China, which seriously threatens the health of people. The application of immunotherapy, mainly immune checkpoint inhibitors, has greatly improved the prognosis of patients with esophageal squamous cell carcinoma, but the efficacy of treatment is still limited. Tertiary lymphoid structure (TLS) is an ectopic organized lymphoid structure that accumulates in non-lymphoid organs. Previous studies have found that TLS in esophageal squamous cell carcinoma is associated with better patient outcomes and enhanced immunotherapy efficacy. Based on current researches about TLS in esophageal squamous cell carcinoma, this paper reviews the relationship between TLS and the prognosis and immunotherapy of patients. We hope to provide reference for the precise immunotherapy of esophageal squamous cell carcinoma.
Non-small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and is an important cause for cancer death. Although the application of immunotherapy in recent years has greatly improved the prognosis of NSCLC, there are still huge challenges in the treatment of NSCLC. The immune microenvironment plays an important role in the process of NSCLC development, infiltration and metastasis, and they can interact and influence each other, forming a vicious circle. Notably, single-cell RNA sequencing enables high-resolution analysis of individual cells and is of great value in revealing cell types, cell evolution trajectories, molecular mechanisms of cell differentiation, and intercellular regulation within the immune microenvironment. Single-cell RNA sequencing is expected to uncover more promising immunotherapies. This article reviews the important researches and latest achievements of single-cell RNA sequencing in the immune microenvironment of NSCLC, and aims to explore the significance of applying single-cell RNA sequencing to analyze the immune microenvironment of NSCLC.
ObjectiveTo explore the relationship between circadian rhythm genes and the occurrence, development, prognosis, and tumor microenvironment (TME) of lung adenocarcinoma (LUAD). MethodsThe Cancer Genome Atlas data were used to evaluate the expression, copy number variation, and somatic mutation frequency of circadian gene sets in LUAD. Gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis were used to explore the potential mechanisms by which circadian rhythm genes affected LUAD progression. Cox regression, least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and random forest screened circadian genes and established prognostic models, and on this basis constructed nomogram to predict patients’ 1-, 3-, and 5-year survival rates. Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model, and the external dataset of GEO further verified the prognostic value of the prediction model. In addition, we evaluated the association of the prognostic model with immune cells and immune checkpoint genes. Single cell RNA sequencing (scRNA-seq) analysis was used to explore the molecular characteristics between prognostically relevant circadian genes and different immune cell populations in TME. ResultsDifferentially expressed circadian rhythm genes were mainly enriched in biological processes related to cGMP-PKG signaling pathway, lipid and atherosclerosis, and JAK-STAT signaling pathway. Seven circadian rhythm genes: LGR4, CDK1, KLF10, ARNTL2, RORA, NPAS2, PTGDS were screened out, and a RiskScore model was established. According to the median RiskScore, samples were divided into a high-risk group and a low-risk group. Compared with patients in the low-risk group, patients in the high-risk group showed a poorer prognosis (P<0.001). Immunological characterization analysis showed that there were differences in the infiltration of multiple immune cells between the low-risk group and high-risk group. Most immune checkpoint genes had higher expression levels in the high-risk group than those in the low-risk group, and RiskScore was positively correlated with the expression of CD276, TNFSF4, PDCD1LG2, CD274, and TNFRSF9, and negatively correlated with the expression of CD40LG and TNFSF15. The scRNA-seq analysis showed that RORA and KLF10 were mainly expressed in natural killer cells. ConclusionThe prognostic model based on seven feature circadian rhythm genes has certain predictive value for predicting survival of LUAD patients. Dysregulated expression of circadian genes may regulate the occurrence, progression as well as prognosis of LUAD through affecting TME, which provides a possible direction for finding potential strategies for treating LUAD from the perspective of mechanism by which circadian disorder affects immune cells.
Objective To summarize the research progress on immune microenvironment imbalance and targeted interventions in osteoarthritis comorbid with diabetes mellitus, so as to provide a reference for the development of disease-modifying therapies and individualized local drug-delivery strategies for this comorbid population. Methods Relevant domestic and international studies published in recent years were reviewed. Focusing on the “oxidative stress-immune interaction” axis, the major alterations and cellular network characteristics of the immune microenvironment in osteoarthritis comorbid with diabetes mellitus were summarized, with emphasis on microenvironment-targeted intervention strategies, including small-molecule drug repurposing, nanodelivery systems, exosome/nucleic acid-based therapeutics, and injectable biomaterials. Challenges and prospects related to stratified diagnosis and treatment, efficacy endpoints, and long-term safety in clinical translation were also discussed. Results The core pathological basis of osteoarthritis comorbid with diabetes mellitus involves hyperglycemia-induced oxidative stress and immunometabolic reprogramming. Through mechanisms such as the accumulation of advanced glycation end products, lipotoxicity, mitochondrial dysfunction, and abnormalities in the gut-joint axis, these changes promote persistent synovitis, extracellular matrix degradation, pain sensitization, and structural joint damage. Immune microenvironment imbalance is mainly characterized by pro-inflammatory polarization of synovial macrophages with impaired efferocytosis, T helper 17 cells/regulatory T cells imbalance, reduced immunomodulatory capacity of mesenchymal stem cells and their exosomes, and senescence-associated immune remodeling in bone marrow lesion areas. Based on these mechanisms, targeted intervention strategies, including small-molecule drug repurposing, nanodelivery systems, exosome/nucleic acid-based therapeutics, and injectable biomaterials, have shown promising application prospects. However, their clinical translation still faces challenges, such as insufficient stratified diagnosis and treatment, inadequate efficacy evaluation systems, and limited long-term safety evidence. ConclusionThe development and progression of osteoarthritis comorbid with diabetes mellitus are closely associated with the persistent interplay among metabolic abnormalities, oxidative stress, and immune microenvironment imbalance. Targeted interventions based on modulation of the local joint microenvironment may relieve pain, improve joint function, and delay the progression of structural joint damage, thereby providing new insights into disease-modifying therapy. Future studies should further refine stratified diagnostic and therapeutic strategies, optimize biomarker selection and delivery platform design, and strengthen long-term safety evaluation to facilitate clinical translation of these strategies.
ObjectiveTo review the research progress regarding the effects of the local microenvironment after meniscal injury and immunomodulatory strategies for meniscal regeneration. MethodsRelevant literature on meniscal regeneration, macrophage polarization, and tissue engineering was retrieved. The mechanisms underlying immune microenvironment imbalance after injury were summarized, and immunomodulatory interventions were analyzed from four perspectives: drugs and bioactive molecules, stem cells and exosomes, biomaterials, and external physical stimuli. ResultsThe highly inflammatory microenvironment dominated by M1 macrophages after injury significantly hinders tissue repair. Current studies mainly promote functional meniscal regeneration through immunomodulatory interventions in four aspects: drugs and bioactive molecules inhibit inflammatory cascades by blocking inflammatory receptors and related signaling pathways; stem cells and exosomes modulate the local immune microenvironment through paracrine effects and enhance the functions of repair-related cells; functionalized biomaterials achieve synergy between immunomodulation and mechanical support through active component delivery, physicochemical property regulation, and structural design; and external physical stimuli, such as acoustic, electrical, and magnetic stimulation, serve as non-invasive auxiliary approaches for inflammation regulation and tissue repair. ConclusionRemodeling the immune microenvironment is critical for functional meniscal regeneration. Smart scaffolds with both mechanical support and immunomodulatory functions should be further developed.
ObjectiveTo summarize recent progress in research on intratumoral and local microbiota associated with gallbladder cancer, with a focus on their potential sources, key microbial taxa, possible mechanisms, clinical implications, and methodological challenges, thereby providing evidence for early identification, risk assessment, and microbiota-based intervention studies of gallbladder cancer. MethodsRecent studies on gallbladder cancer, biliary tract tumors, and tumor-associated microbiota were reviewed, and evidence from bile microbiota, gallbladder mucosa-associated microbiota, and microorganisms detected in tumor tissues was comparatively analyzed. ResultsAvailable evidence suggests that microbiota-associated alterations in gallbladder cancer may be related to retrograde translocation along the gut-biliary axis, hematogenous or portal venous dissemination, and local biliary ecological imbalance. The major taxa reported include Salmonella Typhi, Fusobacterium, Escherichia, Enterococcus, Streptococcus, and Helicobacter. These microorganisms may contribute to gallbladder carcinogenesis through persistent inflammation, DNA damage, bile acid and lipid metabolic reprogramming, immune microenvironment remodeling, and modulation of therapeutic response. However, biliary microbiota, gallbladder mucosa-associated microbiota, and bona fide intratumoral microbiota are not completely equivalent. Low-biomass contamination, host background interference, heterogeneous study designs, and insufficient causal validation remain major limitations in this field. ConclusionsMicrobiota-related research in gallbladder cancer shows potential clinical value, but direct gallbladder cancer-specific evidence is still limited. Future studies should strengthen standardized sampling, multi-omics integration, and functional validation to improve reproducibility and translational relevance.