Objective To investigate whether PLCB1 expression leads to gastric adenocarcinoma metastasis and poor prognosis, and to preliminarily analyze its mechanism. Methods 122 gastric adenocarcinoma patients and their adjacent non-cancerous tissues were selected, and tissue microarray technology was used to detect the expression levels of PLCB1, epithelial cadherin(E-cadherin), vimentin and CD8⁺ T cells by immunohistochemistry, and scored by two pathologists. According to the immunohistochemical score of PLCB1, the patients were divided into PLCB1 high expression group (IHC>90) and PLCB1 low expression group (IHC≤90). The clinical pathological characteristics, epithelial mesenchymal transition(EMT)-related proteins and CD8⁺ T cells expression differences between the two groups were compared. The overall survival of the patients was collected, and COX regression analysis and Kaplan-Meier curve were used to evaluate the relationship between PLCB1 expression level and prognosis. Results PLCB1 was highly expressed in 55 cases of gastric adenocarcinoma tissues, while only 12 cases in adjacent non-cancerous tissues. The tumor invasion depth, lymph node metastasis degree and TNM stage of the PLCB1 high expression group were higher than those of the PLCB1 low expression group. Chi-square test showed that PLCB1 expression level was negatively correlated with E-cadherin (r=-0.339), positively correlated with vimentin (r=0.211), and negatively correlated with CD8⁺ T cells (r=-0.343). Kaplan-Meier curve analysis showed that the overall survival and disease-free survival of gastric adenocarcinoma patients with high PLCB1 expression were significantly reduced. Multivariate COX regression analysis showed that except for lymph node metastasis, tumor invasion depth, TNM stage, E-cadherin and vimentin were also independent prognostic factors for gastric adenocarcinoma patients. Conclusion PLCB1 is highly expressed in gastric adenocarcinoma, and is closely related to tumor aggressiveness and prognosis. PLCB1 may induce EMT and inhibit CD8⁺ T cell infiltration to affect gastric adenocarcinoma metastasis and immune response.
Humans ; Stomach Neoplasms/genetics* ; Epithelial-Mesenchymal Transition ; Male ; Female ; Middle Aged ; Prognosis ; Adenocarcinoma/genetics* ; Cadherins/metabolism* ; Aged ; Adult ; CD8-Positive T-Lymphocytes/immunology* ; Vimentin/metabolism* ; Lymphatic Metastasis ; Neoplasm Metastasis

Chimeric antigen receptor T (CAR-T) lymphocytes are at the forefront of adoptive immunotherapy research, and this technology has significantly advanced the prospects of tumor immunotherapy. CAR-T therapy has demonstrated remarkable efficacy in haematological tumours of lymphoid origin and provided therapeutic possibility for solid tumours. Currently, CAR-T cell preparation predominantly involves transfection of T cells with viral vectors. However, the production of viral vectors is time-consuming, expensive, and the vectors have low loading capacity, along with insertion instability. Consequently, there is a pressing need to develop more convenient and precise non-viral gene delivery methods. This paper reviews the most promising non-viral gene delivery technologies, including CRISPR/Cas9 gene editing, transposon systems such as Sleeping Beauty (SB) and PiggyBac (PB), and mRNA, and anticipates the future development of non-viral vector-based CAR-T therapies.
Humans ; Immunotherapy, Adoptive/methods* ; Receptors, Chimeric Antigen/immunology* ; Animals ; Gene Transfer Techniques ; Genetic Vectors/genetics* ; Gene Editing ; CRISPR-Cas Systems/genetics* ; DNA Transposable Elements/genetics* ; T-Lymphocytes/immunology* ; Neoplasms/immunology*

Myeloid-derived cells (MDCs) are crucial in immune response and tissue homeostasis. They have high functional plasticity and can be polarized according to microenvironment signals. These cells, including macrophages, neutrophils, and dendritic cells (DCs), exhibit different functional polarization states in different pathological environments and are involved in the occurrence and development of diseases such as inflammation and tumors. Studies have shown that metabolic reprogramming plays a key role in the functional polarization of MDCs, affecting the cellular energy supply and regulating immune function. This paper reviews classification, function and polarization mechanism of MDCs and discusses metabolic reprogramming. In addition, the therapeutic strategies targeting MDC are summarized, which is expected to provide new targets for tumor immunotherapy.
Humans ; Tumor Microenvironment/immunology* ; Myeloid Cells/metabolism* ; Neoplasms/pathology* ; Animals ; Immunotherapy/methods* ; Dendritic Cells/immunology* ; Macrophages/immunology*

Objective To explore the expression levels of CD33⁺ myeloid-derived suppressor cell (MDSC)-mediated T lymphocyte function and related inflammatory factors secreted by T lymphocyte subsets in patients with cervical cancer, and to analyze their correlation with the treatment efficacy of ¹²⁵I particle implantation combined with arterial chemoembolization, as well as predictive value for treatment outcomes and interaction effects. Methods From January 1st, 2021 to January 1st, 2024, our hospital admitted 152 patients with advanced cervical cancer, who were confirmed by pathological examination. All patients received uterine artery chemoembolization combined with ¹²⁵I particle implantation. The predictive value of CD33⁺MDSC levels for clinical treatment response in cervical cancer was assessed using receiver operating characteristic (ROC) curve analysis. Multivariate logistic regression analysis was performed to evaluate both multiplicative and additive interactions between CD33⁺MDSC and T lymphocytes in predicting clinical treatment failure of cervical cancer. Kaplan Meier method was used to analyze the survival differences between cervical cancer patients with high and low CD33⁺MDSC expression levels. Results Compared with the effective group, patients in the ineffective group had decreased expression levels of CD3⁺ T lymphocyte, CD4⁺ T lymphocyte, interleukin 2 (IL-2) and interferon γ (IFN-γ), while showing increased expression levels of CD33⁺MDSC, CD8⁺ T lymphocyte, IL-4 and IL-6, along with increased tumor necrosis factor α (TNF-α) levels, larger maximum tumor diameters, and a higher incidence of lymph node metastasis. The expression levels of CD33⁺MDSCs demonstrated good predictive performance for treatment efficacy in cervical cancer patients. The high CD33⁺MDSC expression group had a significantly shorter overall survival (OS) than the low CD33⁺MDSC expression group (6.0±1.0 months vs. 12.0±1.2 months; t=33.280). The interaction analysis revealed that CD33⁺MDSCs and CD8⁺ T lymphocytes were highly expressed, while CD3⁺ and CD4⁺ T lymphocytes were lowly expressed, which was associated with an increased risk of clinical treatment failure in cervical cancer patients. Conclusion CD33⁺MDSCs can inhibit CD3⁺ and CD4⁺ T lymphocytes. It can upregulate the expression of CD8⁺ T lymphocytes, form an immunosuppressive microenvironment, and reduce the treatment response rate of ¹²⁵I particle implantation combined with arterial chemoembolization. CD33⁺MDSCs may serve as an independent biomarker for predicting the therapeutic efficacy and poor prognosis.
Humans ; Female ; Uterine Cervical Neoplasms/immunology* ; Middle Aged ; Chemoembolization, Therapeutic/methods* ; Sialic Acid Binding Ig-like Lectin 3/immunology* ; Adult ; T-Lymphocytes/immunology* ; Aged ; Treatment Outcome

Objective To characterize the properties of Hepa1-6-derived microparticles (Hepa1-6-MPs), investigate their stimulatory effects on dendritic cells (DCs) and their cellular uptake pathways, and explore the specific cytotoxic effects of CD8⁺ T cells induced by Hepa1-6-MP-loaded DCs on hepatoma cell lines, with the aim of developing a novel immunotherapeutic model for hepatocellular carcinoma (HCC). Methods The isolated Hepa1-6-MPs were identified using Western blotting, transmission electron microscopy (TEM) and dynamic light scattering (DLS). Flow cytometry was used to assess the uptake pathways of Hepa1-6-MPs by DCs. Subsequently, enzyme-linked immunosorbent assay (ELISA) was used to measure the effects of Hepa1-6-MP-loaded DCs on the release levels of tumor necrosis factor α(TNF-α) and interferon γ(IFN-γ) into the supernatant of CD8⁺ T cells. Lactate dehydrogenase (LDH) tests were conducted to evaluate the cytotoxic effects of CD8⁺ T cells stimulated by Hepa1-6-MP-loaded DCs on hepatoma cells. Results The morphology, size and protein markers of Hepa1-6-MPs met the established criteria. Hepa1-6-MPs enhanced the expression of DC maturation markers CD80 and CD86, and were internalized by DCs via clathrin-mediated endocytosis and phagocytosis pathways. Subsequently, Hepa1-6-MP-loaded DCs stimulated CD8⁺ T cells to release high levels of TNF-α and IFN-γ, which induced their specific cytotoxicity against HCC cells. Conclusion These findings suggest that Hepa1-6-MP-loaded DCs may be a promising HCC immunotherapeutic tool.
Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Dendritic Cells/immunology* ; Humans ; Cancer Vaccines/immunology* ; CD8-Positive T-Lymphocytes/immunology* ; Cell Line, Tumor ; Tumor Necrosis Factor-alpha/immunology* ; Interferon-gamma/immunology* ; Cell-Derived Microparticles/immunology* ; Animals

Heat shock protein 70 (HSP70), an evolutionarily conserved molecular chaperone, serves as a central regulator within tumor immune networks. This review summarizes the multiple immune regulatory mechanisms mediated by HSP70 through its specific domains: promoting antigen presentation and cross-presentation processes; prolonging immune response duration; regulating innate and adaptive immune responses; and interacting with immune checkpoint molecules like programmed death-1 ligand 1 (PD-L1). In translation of clinical research, HSP70 can serve as a vaccine adjuvant to enhance immunogenicity, while its inhibitors can overcome resistance to immunotherapy. Additionally, membrane-bound HSP70 represents a potential immunotherapeutic target, and its targeting strategies show significant synergistic effects when combined with immune checkpoint inhibitors. However, due to the functional redundancy of the molecular chaperone network, the clinical efficacy of single-agent HSP70 inhibition is limited. In-depth elucidation of HSP70's synergistic regulatory mechanisms within the chaperone interaction network has important implications for developing novel tumor immunotherapy strategies.
HSP70 Heat-Shock Proteins/metabolism* ; Humans ; Immunotherapy/methods* ; Neoplasms/immunology* ; Animals ; B7-H1 Antigen/metabolism*

Patients with metastatic castration-resistant prostate cancer (mCRPC) face poor prognoses due to tumor heterogeneity and drug resistance. Antibody-drug conjugates (ADCs) have been under development for over two decades for mCRPC treatment. Several clinical trials have demonstrated promising antitumor activity and acceptable safety profiles for ADCs in this setting. Among prostate-specific membrane antigen (PSMA)-targeted ADCs, ARX517 demonstrates superior safety and more significant prostate-specific antigen (PSA) reductions compared to earlier agents such as MLN2704, PSMA-ADC, and MEDI3726. ADCs targeting B7-H3, such as MGC018 and DB-1311, have also shown antitumor activity. ADCs targeting other antigens, including six-transmembrane epithelial antigen of the prostate (STEAP)1 (DSTP3086S), trophoblast cell surface antigen (TROP)2 (sacituzumab govitecan), and solute carrier (SLC) 44A4 (ASG-5ME), have shown preliminary antitumor activity in early trials but face challenges with insufficient efficacy or toxicity. Tisotumab vedotin (targeting tissue factor) has shown no significant therapeutic response in mCRPC. Meanwhile, disitamab vedotin (HER2-targeted), ABBV-969 and DXC008 (both dual PSMA/STEAP1-targeted) are currently under evaluation. Notably, an international multicenter phase Ⅲ clinical trial (NCT06925737) for mCRPC has been initiated in May 2025 for evaluating B7-H3-targeted ADC ifinatamab deruxtecan. This review summarizes recent advances in ADCs targeting key antigens in mCRPC (including PSMA, B7-H3, STEAP1, TROP2, SLC44A4, and others) and explores combination strategies, offering insights to inform the clinical management of mCRPC.
Humans ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Male ; Immunoconjugates/therapeutic use* ; Glutamate Carboxypeptidase II/immunology* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; B7 Antigens/immunology* ; Neoplasm Metastasis ; Prostate-Specific Antigen ; Antigens, Neoplasm/immunology* ; Antigens, Surface ; Camptothecin/analogs & derivatives* ; Oxidoreductases

T cell exhaustion plays an immunosuppressive role in malignant tumors. Continuous tumor antigen stimulation, the presence of suppressive immune cells and cytokines in the tumor microenvironment, the up regulation of inhibitory receptor expression on the surface of T cells, changes in T cell related transcription factors, and metabolites in the tumor microenvironment may lead to T cell exhaustion. Reversing the exhaustion of T cells in tumor patients is a promising strategy for tumor immunotherapy. This article will review the latest research progress on T cell exhaustion status, pathogenesis, reversal methods, and clinical applications in hematological tumors.
Humans ; Hematologic Neoplasms/immunology* ; T-Lymphocytes/immunology* ; Tumor Microenvironment ; Immunotherapy ; T-Cell Exhaustion

Lung cancer is one of the most common and lethal malignancies in China. In the context of the tumor microenvironment, neutrophil extracellular traps (NETs) released by neutrophils exert a profound impact on the occurrence and progression of lung cancer. Although the exact mechanisms by which NETs promote tumor growth have not been fully elucidated, existing research has revealed their multiple roles in tumor growth, invasion, metastasis, and cancer-related thrombosis. This article will review the molecular biology mechanisms and research progress of NETs in lung cancer based on recent studies.
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Extracellular Traps/metabolism* ; Humans ; Lung Neoplasms/drug therapy* ; Neutrophils/immunology* ; Animals ; Tumor Microenvironment

The tertiary lymphoid structure (TLS) plays a crucial role in the tumor microenvironment, influencing tumor development and progression. As an emerging biomarker for predicting the prognosis and treatment response in cancer patients, TLS has received increasing attention. However, there is currently a lack of standardized evaluation criteria for TLS, and significant differences exist in TLS across different tumor tissues. This poses challenges for the clinical application of this biomarker in translation. To meet the clinical diagnosis and treatment needs of non-small cell lung cancer (NSCLC), this consensus focuses on the definition, clinical significance, testing components, and assessment methods of TLS in NSCLC. Combining relevant research and Chinese clinical practice, it provides standardized and normalized suggestions for the clinical assessment and application of TLS, so as to improve the understanding of TLS among clinicians and pathologists, and provide a reference basis for the clinical application of the detection of TLS in NSCLC. 
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Humans ; Carcinoma, Non-Small-Cell Lung/immunology* ; Lung Neoplasms/immunology* ; Tertiary Lymphoid Structures/immunology* ; Consensus ; China ; East Asian People