Perturbation of macropinocytosis triggers methuosis, a non-apoptotic cell death characterized by cytoplasmic vacuolization. However, the regulatory mechanisms of methuosis remain poorly defined. Lipid metabolism dysregulation is implicated in various cell death pathways, while its role in methuosis has remained elusive. Herein, LXX-8250, an isopropanolamine derivative of β-elemene, induced a vacuolization-associated cell death in breast and liver cancer cell lines. This process was accompanied by massive macropinocytosis, thereby confirming the occurrence of methuosis. Mechanistically, hypoxia-inducible lipid droplet-associated protein (HILPDA), a key regulator that promotes intracellular triacylglycerol (TAG) accumulation, was identified as the direct target of LXX-8250. By suppressing HILPDA, LXX-8250 inhibited diacylglycerol O-acyltransferase 1 (DGAT1) and activated adipose triglyceride lipase (ATGL). Consequently, lipid droplets and cellular TAG levels were reduced, while the subsequent increased diacylglycerol (DAG) stimulated macropinosome formation, leading to methuosis in these cells. In this study, we discover a novel methuosis agonist LXX-8250, and elucidate the critical role of HILPDA repression-dysregulated lipid metabolism in methuosis. Our study highlighted the potential of targeting this pathway as a therapeutic strategy to trigger cancer cell death.

Objective: To investigate the clinical value of dynamic monitoring of plasma circulating tumor DNA (ctDNA) in evaluating the efficacy of immunotherapy for esophageal squamous cell carcinoma (ESCC). Methods: Plasma samples were collected at baseline and after every 2-3 treatment cycles from 94 patients with advanced ESCC receiving second-line sintilimab monotherapy in the ORIENT-2 study. Targeted sequencing was performed to analyze somatic variants in ctDNA, and the molecular tumor burden index (mTBI) was calculated to assess dynamic changes in ctDNA. Imaging examinations were conducted synchronously with plasma sample collection, and treatment response was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Results: A total of 614 somatic mutations were detected in 93 eligible baseline plasma samples, with a median of 6 mutations per sample. Missense mutations were the most frequent mutation type. The baseline mutational profile revealed frequently mutated genes including TP53 (82%), CDKN2B (23%), and NOTCH1 (22%). In the 68 patients with both baseline and post-2-cycle plasma samples, no significant changes were observed in the variant allele frequencies (VAFs) of core driver genes before and after treatment (all P＞0.05), and no newly emerged core driver gene mutations were identified. CCND1 copy number variation was associated with shorter progression-free survival (PFS) (HR=1.88, 95% CI: 1.08-3.27), while mutations in other genes, including TP53 and NOTCH1, showed no association with PFS (all P＞0.05). None of the frequently mutated genes were associated with overall survival (OS) (all P＞0.05). Among the 68 patients, 11 (15.9%) achieved ctDNA clearance, none of whom showed tumor progression on concurrent imaging evaluation. The remaining 57 patients had ctDNA that became positive or remained persistently positive, of whom 30 (52.6%) showed tumor progression on imaging, with a statistically significant difference between groups (P=0.002). Compared with patients whose ctDNA became or remained positive, those with ctDNA clearance exhibited significantly delayed tumor progression (HR=2.05, 95% CI: 1.06-3.96), but ctDNA status after 2 cycles did not significantly affect OS (HR=1.38, 95% CI: 0.62-3.09). After 2 cycles of treatment, patients in the low mTBI group had a higher disease control rate (DCR) than those in the high mTBI group [73.5% (25/34) vs. 38.2% (13/34), P=0.007], as well as superior PFS (HR=2.80, 95% CI: 1.65-4.75) and OS (HR=3.54, 95% CI: 1.95-6.42). Dynamic changes in mTBI were highly consistent with concurrent imaging response assessments. The molecular response group had a significantly higher DCR than the non-response group [87.5% (21/24) vs. 42.2% (19/45), P＜0.001], as well as superior PFS (HR=2.39, 95% CI: 1.41-4.06) and OS (HR=2.77, 95% CI: 1.46-5.22). Among 32 patients with stable disease (SD) at the first imaging evaluation after 2 cycles, those in the molecular response group had comparable PFS with the non-response group (HR=1.03, 95% CI: 0.51-2.08, P=0.942), but significantly longer OS (HR=3.12, 95% CI: 1.20-8.06). Conclusion: Dynamic monitoring of the ctDNA-based molecular tumor burden index (mTBI) provides real-time and sensitive molecular information for evaluating the efficacy of immunotherapy in advanced ESCC, demonstrating definite clinical value for personalized treatment management.

Objective: To investigate the expression profile of Centromere Protein N (CENPN) in invasive breast cancer (BRCA), evaluate its prognostic significance, and assess its involvement in immune regulation. Methods: The expression, prognostic value, and correlation with tumor immunogenicity of CENPN in BRCA tissues were analyzed based on The Cancer Genome Atlas (TCGA) database. Verification was conducted using cancerous and adjacent normal tissues from BRCA patients who underwent surgical treatment at Yantai Mountain Hospital between January 2022 and April 2023. CENPN expression in various immune cells in the blood was examined using the Human Protein Atlas (HPA) database. Genetic alterations of CENPN in breast cancer tissues were analyzed via the cBioPortal database. CENPN-related genes were screened using the GEPIA 2.0 database, and the interaction network between CENPN and similar genes was visualized with the STRING database. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) were employed to explore the potential biological functions of CENPN. The correlation between CENPN expression and immune cell infiltration, as well as immune cell markers in BRCA tissues, was assessed using the TIMER 2.0 database. The effect of CENPN on the proliferation ability of breast cancer MCF-7 cells was detected by the CCK-8 assay, and its impact on the migration ability of MCF-7 cells was evaluated by a wound healing assay. Results: Analysis of TCGA database data revealed that CENPN expression was significantly higher in BRCA tissues compared to adjacent normal tissues (P＜0.05). Validation in our institutional cohort demonstrated a significantly higher positivity rate for CENPN in the 17 breast cancer tissues (82.4%) than in the paired paracancerous tissues (5.9%, P＜0.001). According to the HPA database, elevated CENPN expression was observed in T-reg cells, naïve B cells, and myeloid dendritic cells. Kaplan-Meier survival analysis indicated that patients with high CENPN expression had poorer overall survival (HR=1.39, P＜0.001), recurrence-free survival (HR=1.31, P＜0.001), post-progression survival (HR=1.28, P=0.036), and distant metastasis-free survival (HR=1.6, P＜0.001). Correlation analysis revealed a negative association between CENPN expression and tumor mutational burden in BRCA patients (r=-0.196, P＜0.001). Furthermore, CENPN expression was positively correlated with 5 out of 20 common immune checkpoint genes and negatively correlated with the remaining 15, suggesting its potential for predicting immunotherapy response. Analysis via the cBioPortal database showed that invasive lobular breast carcinoma had the highest CENPN alteration frequency, with amplification being the most common alteration in BRCA. Invasive mixed mucinous breast carcinoma exhibited the highest mutation frequency, and a key missense mutation (K329N) was identified as a potential driver in BRCA.GO enrichment analysis demonstrated that CENPN-related genes were primarily involved in cell cycle, DNA metabolic processes, cell division, nuclear lumen, chromosomes, nucleoplasm, and functions related to ATP, nucleotide, and small molecule binding. KEGG pathway analysis indicated significant enrichment in DNA replication, cellular senescence, mismatch repair, homologous recombination, p53 signaling pathway, and FOXO signaling pathway. Correlation analysis using the TIMER 2.0 database established associations between CENPN expression and the infiltration levels of B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells in BRCA. Positive correlations were also found with markers for CD8+ T cells, B cells, T cells, and T-cell exhaustion.CCK-8 assay and wound healing experiments confirmed that CENPN knockdown significantly suppressed malignant phenotypes, including proliferation and migration, in MCF-7 cells. Additionally, CENPN knockdown was found to enhance the chemosensitivity of MCF-7 cells to the anti-tumor agents 5-fluorouracil and gemcitabine. Conclusion: CENPN serves as a potential prognostic biomarker and a novel target for immunotherapy in BRCA.

Objective: This study aims to investigate the expression characteristics of GLUT10 in breast cancer and its role in mediating cisplatin resistance, with the goal of providing a new molecular target for personalized breast cancer treatment. Methods: Data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases were analyzed using the GEPIA2 platform to assess pan-cancer expression, while the UALCAN platform was used to analyze expression differences between breast cancer and normal breast tissues. In vitro, SK-BR-3 cells were divided into three groups: shScr (transfected with non-targeting scrambled shRNA), shSLC2A10#1, and shSLC2A10#2. MDA-MB-231 cells were divided into a vector control group and an SLC2A10 overexpression group. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect SLC2A10 mRNA expression. Western blotting was used to detect GLUT10 and cleaved caspase-3 protein expression. The CM-H2DCFDA probe was used to measure intracellular reactive oxygen species (ROS) levels. Drug sensitivity and colony formation assays were performed to evaluate cisplatin sensitivity, and flow cytometry was used to detect apoptosis rates. Results: GEPIA2 analysis showed that GLUT10 expression was downregulated in adrenocortical carcinoma, cervical squamous cell carcinoma and adenocarcinoma, and kidney chromophobe tumor tissues compared to normal tissues, whereas it was upregulated in invasive breast cancer, glioma, skin melanoma, and thymoma. UALCAN analysis revealed that SLC2A10 mRNA levels in breast cancer tissues were 1.85-fold higher than in normal breast tissues (P＜0.001). RT-qPCR results showed that SLC2A10 mRNA expression levels in breast cancer cell lines, ranked from high to low, were Hs 578T (160.5±12.3), SK-BR-3 (115.2±10.5), MDA-MB-468 (50.1±5.2), T-47D (35.4±4.1), and MCF7 (25.6±3.8), all significantly higher than in normal breast epithelial cells (P＜0.001). In SK-BR-3 cells, compared with the shScr group, the shSLC2A10#1 and shSLC2A10#2 groups exhibited increased intracellular ROS levels (relative fluorescence intensity: 1.78±0.12 and 2.05±0.15, respectively; P＜0.05), increased cisplatin sensitivity, reduced colony numbers, and promoted cisplatin-induced ROS accumulation and apoptosis. In MDA-MB-231 cells, compared with the vector control group, the SLC2A10 overexpression group showed decreased intracellular ROS levels (relative fluorescence intensity: 0.58±0.09, P＜0.05), decreased cisplatin sensitivity, and inhibited cisplatin-induced ROS accumulation and apoptosis. Conclusion: GLUT10 is highly expressed in breast cancer and mediates cisplatin resistance by regulating ROS levels, suggesting it may serve as a novel therapeutic target for reversing drug resistance in breast cancer.

Immunotherapeutic approaches for cutaneous squamous cell carcinoma (cSCC) remain limited to programmed cell death protein 1 (PD-1) blockade. Although genomics studies have characterized key driver mutations in cSCC, preclinical models that faithfully recapitulate both the genetic landscape and immune microenvironment of the human disease, that could drive the development of novel, effective therapies, are lacking.

HLA-G is a non-classical MHC class I molecule with potent immunoregulatory functions that is aberrantly expressed in multiple malignancies, yet its tumor-intrinsic role remains poorly defined. To characterize this potential oncogenic role of HLA-G in clear cell renal cell carcinoma (ccRCC), we utilized integrated transcriptomic, in vitro, and in vivo approaches. Analysis of the Cancer Genome Atlas (TCGA) ccRCC cohort revealed that elevated HLA-G expression was associated with immunosuppressive programs and cell populations. Interrogation of a publicly available ccRCC single-cell RNA sequencing dataset revealed that HLA-G expression within tumor epithelial clusters is associated with hypoxia-driven, metabolic transcriptional programs. Multiplex immunofluorescence of human ccRCC specimens confirmed the presence of tumor cell-intrinsic HLA-G expression in advanced disease. Functional studies using RCC7 cells expressing the full-length canonical HLA-G isoform (RCC7/HLA-G1) demonstrated increased proliferation, migration, clonogenicity, cell-cycle progression, and resistance to apoptosis compared with HLA-G-negative RCC7wt cells. RCC7/HLA-G1 xenografts exhibited accelerated tumor growth accompanied by the activation of proliferative, stemness-related, and metabolic programs. Multi-omics analyses further revealed enhanced mitochondrial activity and redox metabolic adaptation in HLA-G-expressing tumors. Mechanistically, HLA-G expression was associated with increased VEGF-C expression and enhanced VEGFR3 signaling, suggesting the activation of a VEGF-C/VEGFR3-associated pro-survival pathway. In three-dimensional tumor spheroid immune cell co-culture models, HLA-G expression reduced CD8⁺ T-cell-mediated cytotoxicity while promoting regulatory T-cell expansion and macrophage polarization toward an immunosuppressive M2-like phenotype. Collectively, these findings establish HLA-G as a key contributor to tumor progression and immune suppression in ccRCC and support HLA-G as a promising therapeutic target.

Homologous recombination repair (HRR) pathway defects are critical drivers of hereditary cancers, yet population-specific prevalence data from India remain limited. Current testing practices disproportionately focus on BRCA1/2, potentially underidentifying patients with other HRR gene variants who could benefit from targeted therapies.

This review shares the ongoing work of the global Worldwide Innovative Network (WIN) Consortium for Precision Medicine to synthesize emerging cancer treatment data and to define the requirements for a common global cancer database that can truly support precision oncology. We performed a narrative review of emerging cancer treatment data, molecular profiling technologies, and existing clinicogenomic databases, focusing on how tumors are characterized, how subgroups are defined, and how demographic, lifestyle, and environmental factors are captured. The growth in molecular profiling technologies and the development of new targeted therapies are transforming cancer care. Tumors, regardless of tissue origin, are increasingly defined as composites of multiple, often rare, subgroups, each with distinct biology and likely response to specific therapies, based on multidimensional profiling of the tumor and its microenvironment. The solution lies in building vast databases that capture racial and ethnic diversity, reflected in genomic data, as well as diet and lifestyle factors that may have epigenetic impact on gene expression and post-translational modifications. A truly inclusive and informative data set must reflect global diversity, and there are multiple examples of demography-dependent differences in genomic signals. With members caring for and studying patients with cancer across five continents, WIN is actively exploring pathways to create a global cancer database, rich in clinical and molecular detail, granular enough for precise analysis, and large enough to power artificial intelligence-driven insights, provided appropriate data quality, validation, and governance frameworks are in place. This review surveys the current landscape and outlines practical paths forward to achieve this goal.

Primary breast neuroendocrine carcinomas (NECs) are rare, high-grade malignancies that are frequently grouped with invasive breast carcinomas with neuroendocrine differentiation (IBC-NED), despite uncertain biological equivalence. We sought to define the clinicopathologic, immunophenotypic, and genomic features of breast NEC and to determine whether they represent a biologically distinct entity.

Diffuse midline gliomas (DMGs) are highly aggressive, WHO grade 4 glial tumors that arise in midline central nervous system structures and are defined by K27M mutations in histone H3 genes. These K27M mutations shape intratumoral myeloid cell composition in DMG. In H3.1K27M DMGs, genetic ablation of monocyte recruitment reshapes the tumor microenvironment (TME) by reducing monocyte-derived macrophages (MDMs) and increasing microglia and neutrophil presence, with overall survival remaining unchanged, indicating compensatory myeloid remodeling is occurring. Here, by using CRISPR/Cas9-based genome editing, we generated a mouse model deficient for CCR1/CCR2/CCR3/CCR5 (Δ1235). Using this strain, we effectively abolished monocyte and MDM infiltration and reversed compensatory recruitment of CCR1+ neutrophils. Abolishing MDMs in tumors skewed remaining neutrophils and microglia toward a homeostatic state, reduced expression of immune checkpoint molecules on T cells, and extended the survival of H3.1K27M DMG-bearing mice. In contrast, H3.3K27M DMG showed independence from MDM recruitment, suggesting reliance on other TME-driven signaling. Last, H3.1K27M DMGs exhibited reduced microglia presence and a dose-dependent increase in MDM infiltration postirradiation. MDM depletion did not further enhance radiation efficacy, potentially due to compensatory recruitment of classical neutrophils. Collectively, these data reveal histone mutation-specific myeloid dependencies in DMG, highlighting MDM-independent mechanisms in H3.3K27M tumors and MDM-dependent pathways in H3.1K27M tumors.

Learning to Rank (LeToR) methods have gained increasing attention in drug response prediction, offering a direct way to prioritize effective treatments for cancer cell lines. In this study, we systematically benchmark six ranking loss functions, including state-of-the-art listwise methods, and five types of molecular representations across two large-scale drug screening datasets, CTRP and PRISM. Using high-dimensional gene expression profiles and various drug fingerprints and descriptors, we evaluated models under multiple validation setups and ranking metrics. Our results demonstrate that listwise loss functions such as LambdaLoss and LambdaRank consistently excel in both early and overall ranking quality. Additionally, combining molecular fingerprints with physicochemical descriptors yielded improved performance. A novel attention-based mechanism and a modified version of RankingSHAP were integrated to enhance interpretability, uncovering key genes and substructures aligned with known biological insights. The explainability pipeline successfully distinguished estrogen receptor-positive (ER⁺) and estrogen receptor-negative (ER-) breast cancer subtypes. The model successfully identified critical substructures in docetaxel, an FDA-approved therapy, and triptolide, which is currently undergoing clinical evaluation for breast cancer. These findings are consistent with established structure-activity relationship (SAR) data. Overall, this study presents a comprehensive evaluation framework and underscores the importance of carefully selecting loss functions and feature representations when developing robust and interpretable drug-ranking systems.

Breast cancer is the most common cancer in women and a leading cause of death. Traditional risk assessment models, such as the Gail model, lack molecular insight, limiting their usefulness for personalized prevention strategies. We developed a computational framework that integrates individual transcriptomic data with dynamic modeling of cell signaling to create personalized models for 30 subjects (including 15 who later developed breast cancer). Using features extracted from the dynamic simulation, we stratified individuals into four risk clusters with significantly different disease-free periods. The highest-risk group had a median disease-free period of 6.05 years, which is significantly shorter than that of the other clusters. This high-risk phenotype was characterized by hyperactive MAPK signaling (high phosphorylated ERK, phosphorylated RSK, and c-Fos). This approach demonstrates that interactions among pathway components provide additional information beyond static gene expression profiles in risk assessment and may serve as a promising tool for guiding personalized prevention strategies.

Smoking cessation decreases lung cancer progression; however, its effects on precancerous lesions and the underlying mechanisms remain unclear. This study established a mouse model of precancerous pulmonary nodules and employed single-cell RNA sequencing (scRNA-seq) and immune repertoire sequencing (IR-seq) to elucidate the regulatory mechanisms by which smoking cessation influences the development of lung precancerous lesions.

This study aimed to links between ATP7B, CTR1, GPX4, 53BP1, p-H2AX and p-ATM expression, platinum sensitivity and prognosis in patients with epithelial ovarian cancer (EOC).

R-loops are three-stranded nucleic acid structures comprising a DNA: RNA hybrid and a displaced single-stranded DNA strand. Their abnormal persistence can trigger transcription-replication conflicts, replication-fork stalling, DNA damage, chromosomal instability, inflammatory signalling, and epigenetic reprogramming. These effects are particularly relevant to colorectal cancer (CRC), which is frequently characterised by replication stress, defective DNA repair, genomic instability, and treatment resistance. This review summarises current evidence linking altered R-loop homeostasis to CRC initiation, progression, metastasis, molecular heterogeneity, and therapeutic response. We discuss key regulators with evidence in CRC or intestinal models, including RNASEH1/2, DDX21, DHX9, TOP1, POLD1/POLD3, and ATR, while distinguishing them from emerging mechanisms requiring CRC-specific validation. We also evaluate major R-loop detection strategies and their limitations. R-loop-associated vulnerabilities may influence responses to irinotecan, ATR/CHK1 and WEE1 inhibitors, PARP-related strategies, and immunotherapy. However, most evidence remains preclinical, highlighting the need for orthogonal detection methods, patient-derived models, and clinically annotated cohorts.

Altered platinum chemotherapy sensitivity is a major determinant of treatment outcome in ovarian cancer; however, the molecular mechanisms underlying adaptive chemotherapy responses remain incompletely understood. Sphingomyelin synthase 1 (SMS1) and sphingomyelin synthase 2 (SMS2), key enzymes involved in sphingomyelin biosynthesis, have been implicated in cancer biology, but their roles in platinum chemotherapy response remain unclear.

Hepatocellular carcinoma (HCC) is a highly aggressive malignancy characterized by unfavorable clinical outcomes. Identifying novel biomarkers and therapeutic targets is essential for advancing HCC management. Although DBF4 zinc finger B (DBF4B) has been associated with the progression of various cancers, its specific role in HCC remains poorly understood.

B-cell acute lymphoblastic leukemia (ALL) with KMT2A rearrangements (KMT2Ar B-ALL) represents a distinct, high-risk subtype in adults, characterized by aggressive disease biology, high relapse rates, and inferior long-term survival. Conventional intensive chemotherapy, even when consolidated with allogeneic hematopoietic stem cell transplantation (allo-HSCT), yields suboptimal outcomes, underscoring the need for novel therapeutic approaches. In recent years, substantial progress has been made with the introduction of antibody-based immunotherapies, cellular immunotherapies, and small molecular inhibitors, reshaping the treatment landscape for this challenging subgroup. This review provides a comprehensive overview of current and emerging therapeutic strategies for adult patients with KMT2Ar B-ALL. We summarize outcomes associated with pediatric-inspired chemotherapy and allo-HSCT, focus on clinical evidence for antibody-based immunotherapy including blinatumomab and inotuzumab ozogamicin, across frontline, consolidation, and relapsed or refractory settings. Advances in cellular immunotherapy, particularly CD19-directed chimeric antigen receptor T-cell therapy, are discussed, with a focus on unique resistance mechanisms such as antigen loss and lineage switch. In addition, we review the biological rationale, efficacy and emerging resistance mechanisms of menin inhibitors, a promising class of agents specifically targeting the epigenetic dependency of KMT2A-rearranged leukemia. Finally, other molecular approaches, including epigenetic modifiers, apoptosis pathway inhibitors, and signaling pathway inhibitors are discussed. Despite these advances, treatment resistance and disease relapse remain major obstacles. These ongoing challenges highlight the urgent need for multi-center, prospective trials to investigate rational combination strategies to improve outcomes for adults with KMT2Ar B-ALL.

MicroRNA-205 (miRNA-205) has been identified as a promising biomarker, yet its clinical application is hindered by the lack of detection strategies that combine simplicity, ultrahigh sensitivity, and high specificity. To address these obstacles, we introduced an innovative biosensor integrating hybridization chain reaction (HCR) with two-dimensional CoOOH nanosheets for precisely detecting the colorectal cancer biomarker miRNA-205 (HCR-CoOOH system). This system took advantage of the preferential binding of CoOOH nanosheets for single-stranded DNA over double-stranded DNA, along with HCR for signal amplification. Without the target miRNA-205, hairpin probes H1 and H2 were adsorbed onto CoOOH nanosheets, resulting in effective FRET-based quenching of the intercalated SYBR Green I fluorescence. In contrast, introduction of the target triggered the HCR cascade, producing numerous long double-stranded DNA polymers. Low affinity between these duplexes and the nanosheets allowed substantial fluorescence recovery under isothermal conditions. A strong linear relationship was observed between fluorescence recovery and miRNA-205 concentration over 0.1-500 nM, with a detection limit of 0.062 nM. Furthermore, the system demonstrated excellent specificity and robust performance in serum samples. Notably, this work circumvented the issues of tedious handling and strong background interference by enabling a swift switch from the "signal-off" to the "signal-on" detection mode, while also simplifying the workflow and reducing non-specific signals. Furthermore, the use of SYBR Green I eliminated the need for covalent fluorophore labeling, markedly reducing assay cost. This versatile strategy provides a valuable new tool for colorectal cancer research and clinical diagnostics.

Immune escape is a hallmark of cancers, which affects the efficacy of immunotherapy. Herein, this study analyzed the significance of GATA1/FGL1 in the immune escape of cervical squamous cell carcinoma (CESC) to deepen the understanding of immune escape-associated molecular mechanisms. In silico analysis predicted the correlations of FGL1 with CESC prognosis and CD8+ T cell infiltration as well as the relation between FGL1 and GATA1. After FGL1 and/or GATA1 gain- and loss-of-function, CC cells were co-cultured with CD8+ T cells. The sensitivity of CC cells to CD8+ T cells was assessed, as well as the secretion of perforin, GzmB, IFN-γ, and TNF-α. Also, CD8+ T cell proliferation and apoptosis were measured. The binding of GATA1 to the FGL1 promoter was validated through luciferase and ChIP assays. GATA1-knockdown U14 cells were transplanted into immunocompetent C57BL/6 mice in combination with or without CD8α mAb to ascertain the impacts of GATA1 on tumor growth and immune escape in CESC in vivo. Knockdown of either FGL1 or GATA1 markedly enhanced the sensitivity of CC cells to CD8+ T cell‑mediated cytotoxicity and increased the secretion of perforin, GzmB, IFN‑γ, and TNF‑α. It also promoted CD8+ T cell proliferation while reducing their apoptosis. These effects of GATA1 knockdown were partially negated by FGL1. In vivo, GATA1 knockdown prominently diminished the tumor growth and increased the infiltration and cytotoxic effects of CD8+ T cells. Collectively, GATA1 knockdown facilitates CD8+ T cell responses and suppresses immune escape in CESC by downregulating FGL1.