Chimeric antigen receptor-natural killer (CAR-NK) cells represent a breakthrough in cancer immunotherapy, making this a highly popular research area. However, comprehensive analyses of this field using bibliometric methods are rare. To our knowledge, this study has collected highest number of publications (1,259) on CAR-NK therapy from January 1, 2004, to December 31, 2023, and utilized CiteSpace and VOSviewer to analyze regions, institutions, journals, authors, and keywords to forecast the latest trends in CAR-NK therapy research. The United States and China, contributing over 60% of publications, are the primary drivers in this field. The Helmholtz Association and Harvard University are the most active institutions, with most publications appearing in Frontiers in Immunology. Winfried S. Wels is the most prolific author, while EL Liu is the most frequently co-cited author. “Immunotherapy,” “T-cells,” and “Cancer” are the most extensively covered topics in CAR-NK therapy research. Our study reveals current CAR-NK research trends, identifies potential research hotspots, and visualizes references through bibliometric methods, providing valuable guidance for future research in this field.

The use of chimeric antigen receptor (CAR) in natural killer (NK) cells for cancer therapy is gaining momentum, marking a significant shift in cancer treatment. This review aims to explore the potential of CAR-NK cell therapy in cancer immunotherapy, providing a fresh perspective. It discusses the innovative approaches in CAR-NK cell design and engineering, particularly targeting refractory or recurrent cancers. By comparing CAR-NK cells with traditional therapies, the review highlights their unique ability to tackle tumor heterogeneity and immune system suppression. Additionally, it explains how novel cytokines and receptors can enhance CAR-NK cell efficacy, specificity, and functionality. The review underscores the advantages of CAR-NK cells, including reduced toxicity, lower cost, and broader accessibility compared to CAR-T cells, along with their potential in treating both blood cancers and solid tumors.

Lung squamous cell carcinoma (LUSC) is associated with poor clinical prognosis and lacks available targeted agents. GPC3 is upregulated in LUSC. Our study aimed to explore the roles of GPC3 in LUSC and the antitumor effects of HLA-A2-restricted GPC3 antigenic peptide-sensitized dendritic cell (DC)-induced cytotoxic T lymphocytes (CTLs) on LUSC. LUSC cells with GPC3 knockdown and overexpression were built using lentivirus packaging, and cell viability, clone formation, apoptosis, cycle, migration, and invasion were determined. Western blotting was used to detect the expression of cell cycle-related proteins and PI3K-AKT pathway-associated proteins. Subsequently, HLA-A2-restricted GPC3 antigenic peptides were predicted and synthesized by bioinformatic databases, and DCs were induced and cultured in vitro. Finally, HLA-A2-restricted GPC3 antigenic peptide-modified DCs were co-cultured with T cells to generate specific CTLs, and the killing effects of different CTLs on LUSC cells were studied. A series of cell function experiments showed that GPC3 overexpression promoted the proliferation, migration, and invasion of LUSC cells, inhibited their apoptosis, increased the number of cells in S phase, and reduced the cells in G2/M phase. GPC3 knockdown downregulated cyclin A, c-Myc, and PI3K, upregulated E2F1, and decreased the pAKT/AKT level. Three HLA-A2-restricted GPC3 antigenic peptides were synthesized, with GPC3_522-530 FLAELAYDL and GPC3_102-110 FLIIQNAAV antigenic peptide-modified DCs inducing CTL production, and exhibiting strong targeted killing ability in LUSC cells at 80:1 multiplicity of infection. GPC3 may advance the onset and progression of LUSC, and GPC3_522-530 FLAELAYDL and GPC3_102-110 FLIIQNAAV antigenic peptide-loaded DC-induced CTLs have a superior killing ability against LUSC cells.

Background: Endometriosis (EM) is associated with immune dysregulation, while dysfunction of natural killer (NK) cells is regarded as a key mechanism underlying immune escape and the persistent growth of ectopic lesions. Method: This study used single‐cell RNA sequencing (scRNA‐seq) on lesions from three patients with EM and on three normal endometrium samples and integrated these data with three bulk RNA‐seq datasets from GEO (GSE105765, GSE7305, and GSE6364). Seurat, Monocle, limma, least absolute shrinkage and selection operator (LASSO), and support vector machine recursive feature elimination (SVM‐RFE) were used for cell clustering, trajectory inference, differential expression analysis, and feature selection. Immune‐cell composition and pathway activity were evaluated with CIBERSORT and GSVA. Gene expression was validated by qPCR, and cell migration and invasiveness were assessed using wound healing and Transwell assays. Result: scRNA‐seq resolved 11 clusters assigned to eight major cell types. By integrating pseudotime features with bulk data, 20 differentially expressed genes (DEGs) were prioritized, and machine‐learning analyses identified three key genes: granulysin (GNLY), perforin 1 (PRF1), and ENTPD1. The three‐gene model showed good discrimination in the training set and two external validation cohorts (AUCs 0.84, 0.67, and 0.77, respectively). GNLY and PRF1 were predominantly expressed in NK cells and CD8 ⁺ T cells and correlated with activation signatures, whereas ENTPD1 was highly expressed in endometrial stromal cells and enhanced their migratory and invasive capacities. ENTPD1 may contribute to disease via adenosine signaling–mediated modulation of NK–cell function. In silico analyses also nominated candidate agents targeting this pathway, including resveratrol, ibuprofen, and danazol. Conclusion: This study highlights the central role of NK–cell dysfunction in EM pathogenesis and proposes GNLY, PRF1, and ENTPD1 as potential molecular diagnostic biomarkers. Notably, ENTPD1 appears to have dual functions, including immunomodulation and promotion of stromal cell migration, which promotes lesion formation. These findings provide a mechanistic rationale and actionable targets for earlier screening and targeted therapy in EM.

The online version contains supplementary material available at 10.1007/s10238-026-02124-4.

Immune checkpoint blockade has changed the therapeutic landscape of cervical cancer, but clinical benefit remains heterogeneous and difficult to predict with single biomarkers. Cervical cancer is a particularly suitable setting for immune-cell profiling because HPV-driven antigenicity, chemoradiotherapy-induced tissue remodeling, anti-angiogenic combinations, and repeated exposure to PD-1/PD-L1 inhibitors all shape the blood-tumor immune axis. This Mini Review discusses how circulating immune cells and tumor-infiltrating immune cells can be jointly interrogated by multi-omics technologies to identify biomarkers of response and resistance. We focus on single-cell RNA sequencing, T-cell receptor/B-cell receptor (TCR/BCR) profiling, cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), flow cytometry, spatial transcriptomics, high-plex spatial proteomics, bulk transcriptomics, cytokine profiling, and circulating tumor DNA (ctDNA)-informed longitudinal designs. Recent cervical cancer atlases suggest that response is unlikely to be explained by total immune infiltration alone, but instead reflects the spatial organization and functional states of cytotoxic T cells, NK cells, antigen-presenting cells, tertiary lymphoid structure (TLS) programs, regulatory T cells, myeloid cells, and cancer-associated fibroblasts (CAFs). We propose a blood-to-tumor framework in which dynamic peripheral phenotypes may monitor systemic immune competence, while tissue multi-omics may identify local immune exclusion, terminal exhaustion, and myeloid suppression. Prospective paired sampling and interpretable, externally validated AI-assisted computational integration are needed before these biomarkers can guide treatment selection.