Glutamine metabolism provides energy and raw materials for tumor survival and proliferation. In addition to affecting cancer cells, many studies have investigated the role of glutamine metabolism on the tumor microenvironment in depth. The macrophages, which show high frequently distribution in the majority of solid tumors, are important immune cells in the tumor microenvironment. Tumor-associated macrophage metabolic network remodeling is enormous and complicated. This review links TAM with glutamine metabolism, and combs the network relationship between the unique functional state of macrophages and the key programs of glutamine metabolism in terms of epigenetic modification, signaling pathway transduction, and metabolic checkpoint regulation. In addition, we will summarize the existing glutamine metabolism-targeting drugs and explore the new technologies and strategies for glutamine metabolism to regulate the functional state of TAM.

This study aims to define a novel molecular subtype of LUAD by integrating multiple omics data. Additionally, we develop and validate an Artificial Intelligence Derived Prognostic Index (AIDPI) that predicts the prognosis of LUAD patients, identifies potential therapeutic targets.

This study employed ten clustering algorithms from the R package "MOVICS" to integrate multi-omics data of LUAD sourced from TCGA database for molecular typing. Subsequently, an Artificial Intelligence Derived Prognostic Index (AIDPI) was constructed as the most effective indicator for predicting the overall survival rate of LUAD patients. The biological functions and mechanisms of NPC2 in lung adenocarcinoma were elucidated through both in vitro and in vivo experiments, which included CCK-8 assays, colony formation assays, flow cytometry, Transwell assays, and xenograft tumor models. Additionally, the impact of NPC2 on Ribociclib sensitivity was investigated through drug correlation analysis and molecular docking, while the predictive value of NPC2 regarding immunotherapy benefits was validated using the immune cell infiltration analysis.

Through multi-omics clustering, we identified two subtypes of lung adenocarcinoma associated with prognosis, with the CS1 subtype exhibiting the most favorable prognostic outcomes. The low AIDPI group exhibited a more positive prognosis, accompanied by increased immune cell infiltration and activation of immune pathways. Meanwhile, NPC2 was recognized as a standalone risk factor for LUAD, with its high expression significantly improving the overall survival of LUAD patients. Functionally, the overexpression of NPC2 promotes tumorigenesis in LUAD both in vitro and in vivo. Mechanistically, the upregulation of NPC2 expression inhibits the progression of LUAD by suppressing the PI3K/AKT signaling pathway. Our study also demonstrated that high NPC2 expression is positively correlated with Ribociclib sensitivity, as confirmed by in vitro experiments. Furthermore, NPC2 expression is positively correlated with ImmuneScore, and may serve as a predictive indicator for the efficacy of immune checkpoint inhibitor (ICI) therapy.

The comprehensive analysis of multiple omics data significantly enhances the molecular classification of lung adenocarcinoma. Furthermore, AIDPI is a potential biomarker that predicts the prognosis of LUAD patients. NPC2 inhibits the progression of LUAD by suppressing the PI3K/AKT signaling pathway and enhancing the chemotherapy sensitivity to Ribociclib.

Paired immunoglobulin-like type 2 receptor alpha (PILRA) is a membrane-associated receptor involved in immune regulation and signal transduction. However, its expression and functional role in breast cancer remain largely unknown. This study investigated the expression, mutation, and DNA methylation patterns of PILRA in breast cancer, along with its impact on immune infiltration and associated pathways. We also evaluated its potential as a therapeutic target for predicting prognosis and guiding immunotherapy in breast cancer.

PILRA expression in breast cancer was analyzed using TCGA and GTEx datasets. Protein expression in breast cancer and adjacent normal tissues was evaluated by immunohistochemistry, and expression levels were validated by RT-qPCR in 50 paired tumor and adjacent tissue samples. cBioPortal was used to assess mutation profiles and prognostic relevance. Associations with drug resistance were examined by analyzing relationships to resistance- and sensitivity-related genes. DNA methylation and its prognostic impact were analyzed using MethSurv. The prognostic and diagnostic value of PILRA was evaluated through survival and ROC curve analyses. Single-cell and tissue expression data were obtained from HPA and GTEx, and gene effect score from DepMap. Immune associations were assessed using TISIDB. Gene correlation and protein-protein interaction networks were analyzed via TCGA and STRING, followed by KEGG and GO enrichment.

PILRA expression was upregulated in breast cancer tissues and associated with poor survival and drug resistance. We identified R236M as the dominant mutation site and found that its mutation is linked to improved prognosis. PILRA methylation downregulated its expression and correlated with better prognosis. Survival analysis and ROC curves supported the potential of PILRA as a prognostic biomarker. PILRA was involved in immune infiltration and modulated the abundance of various immune cells and the tumor microenvironment, suggesting a role in immune regulation and tissue maintenance. Correlation and enrichment analyses revealed that PILRA-associated genes were mainly involved in cancer-related processes and pathways, with key hub genes in the PPI network.

We identified PILRA as a diagnostic and prognostic biomarker in breast cancer and analyzed its association with immunotherapy response. The findings provide new insight and potential strategies for breast cancer diagnosis and treatment.

Breast cancer (BC) is the most common malignant tumor in women, driven by various factors. Its incidence has been rising annually and has become an urgent global public health challenge. An increasing body of evidence suggests that the immune microenvironment (IME) of breast cancer plays a crucial role in tumor initiation, progression, and metastasis. Through multi-target and multi-pathway regulatory effects, Traditional Chinese Medicine (TCM) demonstrates unique potential in reshaping the tumor immune microenvironment (TIME). This narrative review aims to systematically organize and summarize recent mechanistic advancements, elucidating how Traditional Chinese Medicine (primarily based on Chinese herbal medicine) regulates the function and polarization of key immune cells, controls immune checkpoints and cytokine networks, thereby inhibiting tumor immune escape, enhancing anti-tumor immunity, and exerting anti-BC effects. Despite the promising prospects, the application of TCM in BC immunotherapy still faces numerous challenges, including tumor heterogeneity, dosage complexity, and safety issues. Future research should focus on large-scale, multi-center clinical trials combining contemporary immunotherapy strategies, aiming to achieve better clinical outcomes in BC treatment and provide insights for immunotherapy of other cancer types.

Dysregulated expression of long non-coding RNAs (lncRNAs) has been shown to play a critical role in the tumorigenicity of clear cell renal cell carcinoma (ccRCC). Meanwhile, sialylation plays a pivotal role in cancer progression and in modulating the tumor immune microenvironment. However, how sialylation-immune-related lncRNAs (SIRLs) influence tumor immune microenvironment and progression of ccRCC remains unclear.

Using comprehensive cancer datasets, we identified key lncRNAs linked to both sialylation and immune modulation, constructing a prognostic risk model centered on the hub gene LINC01605.

Patients classified as high-risk showed significantly poor survival outcomes and poor response to anti-PD-1 immunotherapy compared to low-risk individuals. Functional studies established LINC01605's role in enhancing tumor aggressiveness and CD8⁺ T cell exhaustion. Knockdown of LINC01605 reduces total sialic acid levels in ccRCC cell membranes. Mechanistically, LINC01605 recruits IGF2BP2 to increase the stability of JAK3 mRNA. Elevated JAK3 expression activates JAK3/STAT3 signaling, and phosphorylated STAT3 subsequently upregulates oncogenes (e.g., MYC) as well as sialyltransferase ST6GALNAC5-which directly increases cell membrane sialylation, a known driver of immune evasion.

Our findings reveal the role of sialylation-immune-related lncRNAs in the immunosuppressive tumor microenvironment and cancer progression in ccRCC, providing a new framework for predicting patient outcomes and therapeutic responses.

Colorectal cancer (CRC) remains a major global health burden. While precision therapies like anti-PD-1 and anti-EGFR antibodies show remarkable efficacy, their application is constrained by stringent biomarker requirements, limiting patient benefit. Diverse animal models-including chemically induced, genetically engineered, and transplantation-based systems-have advanced our understanding of CRC pathogenesis but exhibit limited power in predicting therapeutic outcomes for defined patient subgroups. A central challenge is their imperfect recapitulation of key aspects of human CRC biology, specifically anatomical tumor localization, faithful representation of the tumor immune microenvironment (TME), and a frequent lack of rigorous molecular characterization. This gap underscores the urgent need for advanced models that better mirror human disease to support translational research. This review critically evaluates the establishment, advantages, and limitations of prevalent CRC models, focusing on their capacity to replicate key immunological features of human CRC, such as the complex immune landscape and response to immunotherapies. We examine how discrepancies in anatomical site, immune cell composition, and host immunity between animal models and human patients compromise predictive accuracy, particularly for evaluating immune-checkpoint inhibitors (ICIs) in microsatellite-stable (MSS) tumors. By synthesizing these critiques, we aim to provide a framework for developing immunologically relevant models to accelerate the discovery of effective, personalized immunotherapies for CRC.

Metabolic reprogramming is not only one of the malignant characteristics of tumor cells, but also commonly seen in a variety of immune cells in tumor microenvironment(TME), which massively promotes tumor-body immune interaction. Immunometabolic editing is a dynamic, co-evolutionary process wherein adaptive metabolic reprogramming in the TME, driven by tumor-immune crosstalk during immunoediting, critically shapes anti-tumor immune response and governs immune evasion. Studies of metabolic pathways linked to anti-tumor immune process and discoveries of important therapeutic targets are conducive to the development of targeted immunometabolic intervention to enhance the body's anti-tumor immune response and improve the efficacy of tumor immunotherapies. This review summarizes metabolic characteristics of the TME, highlights immunometabolic editing during cancer evolution, and discusses mechanisms by which tumor immunotherapies modulate tumor immunometabolism to identify potential therapeutic targets.

Chimeric antigen receptor (CAR) T cells show limited efficacy in solid tumors. Oncolytic viruses (OVs), especially those expressing immunomodulatory cytokines like interleukin-12 (IL-12), potentiate to synergize with CAR-T therapy.

We integrated an IL-12-expressing oncolytic herpes simplex virus type 2 (oHSV-2-IL-12) with mesothelin-targeting SS1-ICOSBBZ-CAR-T to treat Capan-2 pancreatic cancer cells xenografts in B-NDG immunodeficient mice.

SS1-ICOSBBZ-CAR-T alone exhibited partial anti-tumor activity, but could not eradicate established tumors. Intra-tumoral oHSV-2-IL-12 administration potently enhanced CAR-T efficacy, achieving complete and durable tumor elimination even at reduced CAR-T doses. After the initial tumors were fully eliminated by combination therapy, mice were re-challenged by inoculating mesothelin-negative and mesothelin-positive tumor cell lines on the left and right flanks, respectively. In the combination treatment group, mesothelin-positive tumors failed to form new tumors within two weeks after re-challenge, whereas mesothelin-negative tumors grew normally. These findings indicate that oHSV-2-IL-12 combined with CAR-T therapy confers durable, antigen-specific protection against tumor re-challenge. Mechanistically, oHSV-2-IL-12 promoted CAR-T proliferation and persistence in peripheral blood and spleen. IL-12 expression also augmented the direct oncolytic effect of oHSV-2 in immunodeficient hosts.

This synergistic approach achieves durable potent tumor clearance with reduced CAR-T doses, offering a transformative strategy against pancreatic cancer and other challenging solid malignancies.

β-Hydroxybutyrylation (Kbhb) is a novel posttranslational modification (PTM) mediated by β-hydroxybutyrate (BHB). BHB, the core product of ketogenic metabolism, serves as its direct precursor and substrate. As a hub connecting energy metabolism and the epigenetic network, Kbhb exerts bidirectional regulatory effects on abnormal tumour metabolism, cardiovascular and cerebrovascular diseases, immune regulation, and other processes. Furthermore, Kbhb is not limited to histones; it is also widely present in nonhistones and influences various biological processes, such as protein stability, metabolic and energy homeostasis regulation, pathogen virulence regulation, transcriptional regulation, and signal transduction. This review summarizes the research progress in the field of Kbhb, including the inducers of Kbhb (ketogenic diet), prediction methods for modification sites (KbhbXG, pFunK, SLAM, iBhb-Lys), regulatory elements of modification (regulatory enzymes such as ENL and SIRT6, and protein substrates), mechanisms of action in cancer (e.g., mTOR signalling pathway, cGAS-STING signalling pathway), mechanisms of action in immune-related signalling pathways and immune-active components regulation, research progress on histone and nonhistone Kbhb (e.g., Bcl6, P53, STAT1, UvSlt2), and novel therapeutic strategies for diseases based on Kbhb modification (metabolic regulation and targeted therapy), providing new insights for targeted therapy for cancer and other diseases.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is a critical mechanism of DNA sensing in innate immunity. Activation of this pathway can induce the production of interferons and proinflammatory cytokines. In the intestine, this pathway exhibits bidirectional regulatory properties, with appropriate activation maintaining homeostasis and inhibiting tumorigenesis, while excessive activation leads to inflammatory responses. A thorough exploration of the molecular mechanisms and regulatory networks of the cGAS-STING signaling pathway offers a significant theoretical foundation and potential treatment targets for developing novel strategies to treat intestinal diseases. This review summarizes the most recent developments on the function of the cGAS-STING regulatory pathway in colorectal tumors and inflammatory bowel disease. It discusses targeted therapeutic approaches that interfere with this pathway.