Cancer Communications癌症通讯
Cancer Communications(英文缩写 CANCER COMMUN),ISSN 2523-3548,eISSN 2523-3548,中文译名:癌症通讯 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-09-27 至 2026-09-27，按本站收录文献的发表日期统计。
期刊介绍
Cancer Communications 最新收录文献
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1. Beyond Structure: The Dynamic Role of the Extracellular Matrix Components in Immune Evasion.
PMID:日期:2026-01-01The extracellular matrix (ECM) is a dynamic and functionally active component of the tumor microenvironment that critically regulates immune cell trafficking, activation, and persistence. Rather than serving solely as a structural framework, ECM remodeling through collagen reorganization, proteoglycan-dependent chemokine sequestration, and fibroblast-driven matrix stiffening actively contributes to immune exclusion and evasion in solid tumors. This review integrates emerging mechanistic insights into how ECM composition, architecture, and mechanical properties shape spatial immune exclusion, T cell dysfunction, and immune-checkpoint regulation through mechanotransduction, metabolic reprogramming, and altered cytokine and chemokine signaling. Particular emphasis is placed on the coordinated activities of distinct ECM components and cancer-associated fibroblast subtypes in establishing spatially restricted immunosuppressive niches that limit antitumor immunity and therapeutic responsiveness. ECM-targeted therapeutic strategies are critically evaluated by integrating their mechanistic rationale, preclinical efficacy, clinical trial outcomes, and current stage of translational development. The importance of biomarker-guided patient stratification is also highlighted for identifying tumors most likely to benefit from ECM-directed interventions, particularly in combination with immune-checkpoint blockade and other immunotherapies. Finally, recent advances in spatial transcriptomics, proteomics, matrix imaging, and ECM-derived circulating biomarkers are discussed as tools to refine therapeutic targeting, monitor matrix remodeling, and predict treatment response. By conceptualizing the ECM as an active immunoregulatory network rather than a passive physical barrier, the review provides a mechanistic and translational framework for developing next-generation, ECM-informed cancer immunotherapies.
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2. Stress Biology in Cancer: Neuroendocrine-Immune Mechanisms Linking Tumor Progression to Translational Interventions.
PMID:日期:2026-01-01Chronic stress-responsive signaling has emerged as a modifiable dimension of cancer biology by linking systemic neuroendocrine activation to tumor-cell adaptation, metabolic rewiring, immune suppression, tumor microenvironment remodeling, metastatic dissemination, and therapeutic resistance. Persistent activation of the sympathetic nervous system (SNS) and the hypothalamic pituitary adrenal (HPA) axis elevates catecholamines and glucocorticoids, which act through adrenergic receptors and the glucocorticoid receptor (GR) in tumor, stromal, vascular, and immune compartments. These canonical pathways regulate cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling, GR-dependent transcription, angiogenic and inflammatory programs, extracellular matrix remodeling, myeloid polarization, T cell dysfunction, and resistance to cytotoxic and immune-based therapies. Beyond this classical SNS/HPA framework, emerging evidence indicates that cancer cells also engage noncanonical stress-adaptive hubs, including ion-channel signaling, redox-dependent mitochondrial responses, integrated stress-response pathways, prolactin/prolactin receptor signaling, and neurotrophin-mediated tumor-stroma-nerve crosstalk. These mechanisms are particularly relevant in highly plastic and immunogenic tumors such as melanoma, where stress adaptation intersects with immune visibility, metabolic flexibility, and therapy response. In this review, we synthesized how chronic stress signaling operates across systemic, tumor-intrinsic, immune, stromal, vascular, metabolic, and neural niches. We further mapped cancer-specific mechanisms across major malignancies and evaluated translational strategies, including β- and α-adrenergic blockade, GR modulation, stress-reducing behavioral interventions, and combination approaches with immunotherapy or standard anticancer regimens. Moreover, we discussed clinical challenges, including heterogeneity in stress exposure, context-dependent receptor activity, sex-specific stress biology, evidence maturity, and the need for biomarker-guided patient stratification. This integrated framework supports the development of mechanism-based stress-targeted adjunctive therapies in oncology.
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3. {"_":"NBR1-Mediated Autophagic Degradation of YTHDF1 Curtails Translation to Drive Concurrent Multikinase Inhibitor Resistance and Cuproptosis Tolerance.","i":["FDX1"]}
PMID:日期:2026-01-01Cancer cells frequently acquire adaptive resistance to targeted therapies; however, strategies capable of concurrently overcoming treatment tolerance and reactivating cell death pathways are currently lacking. Here, we investigated the dual role of ferredoxin 1 (FDX1) in modulating both multikinase inhibitor (MKI) sensitivity and cuproptosis susceptibility in hepatocellular carcinoma (HCC), and sought to develop a therapeutic approach for reversing resistance. HCC models, both in vitro and in vivo, were employed to investigate the role of FDX1 in MKI resistance and cuproptosis evasion. Polysome profiling, SunTag translation reporters, CRISPR-Cas9 mutagenesis, and mass spectrometry were employed to delineate the underlying mechanisms. A codelivery nanoliposome system was engineered and tested in orthotopic HCC models. Prolonged exposure to MKIs led to the down-regulation of FDX1 protein levels, resulting in MKI resistance and cuproptosis tolerance in HCC both in vitro and in vivo. Mechanistically, we found that MKIs inactivated protein kinase B (PKB, also known as AKT)-mechanistic target of rapamycin (mTOR) signaling, thereby suppressing the SET and MYND domain-containing protein 2 (SMYD2)-mediated methylation of YTH domain family protein 1 (YTHDF1) at lysine 515 (K515). Hypomethylated YTHDF1 was degraded via next to BRCA1 gene 1 protein (NBR1)-dependent autophagy, leading to the repression of N6-methyladenosine modification-dependent translation of mRNA. FDX1 deficiency drove MKI resistance by reactivating AKT survival signaling while impairing cuproptosis through reduced divalent copper ions (Cu) to monovalent copper ions (Cu) conversion and the loss of protein lipoylation. Additionally, restoring FDX1 expression through knockdown or overexpression overcame MKI resistance and resensitized HCC cells to cuproptosis. Finally, a nanoliposomal system, super cuproptosis detonator liposome, designed for the codelivery of small interfering RNA, a copper ionophore, and sorafenib restored FDX1-dependent cuproptosis and exhibited marked anti-HCC efficacy, suppressing HCC growth in vivo. MKIs suppressed SMYD2-mediated YTHDF1 methylation at K515 via the inactivation of AKT-mTOR signaling. This led to the inhibition of translation, resulting in AKT signaling reactivation and protein lipoylation impairment, effects that contributed to both MKI resistance and cuproptosis tolerance in HCC. Overcoming MKI resistance and resensitizing cells to cuproptosis by targeting NBR1-mediated YTHDF1 degradation using a nanoliposomal codelivery system represents a promising strategy for HCC treatment.
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4. {"_":"Neutrophil Senescence Induced by Tumor-Derived HMGB1 Promotes Hepatocellular Carcinoma Progression through Neutrophil Extracellular Trap-Mediated Suppression of CD8 T Cell Immunity.","sup":["+"]}
PMID:日期:2026-01-01Immune cells are essential components of the tumor microenvironment. Among them, neutrophils have gained increasing interest due to their marked heterogeneity. This study focused on aged neutrophils, aiming to uncover their mechanistic contribution to hepatocellular carcinoma (HCC) progression and evaluate their potential clinical importance. This study included analyses of 2 public datasets (GSE149614 and GSE189903) as well as a clinical cohort comprising 105 patients with HCC and 41 healthy controls. The abundance of aged neutrophils and CD8 T cells as well as their clinical correlation were assessed, and their potential clinical value was explored. In vitro cellular experiments were used to dissect the molecular mechanisms responsible for CD8 T cell suppression by aged neutrophils and the progression of neutrophil senescence. In addition, a variety of in vitro and in vivo experiments were performed to evaluate the involvement of aged neutrophils in HCC progression. Peripheral blood and tumor tissues from HCC patients exhibited a marked accumulation of aged neutrophils, which was inversely correlated with CD8 T cell abundance. Aged neutrophils released excessive neutrophil extracellular traps (NETs) via a caspase-3-dependent mechanism, thereby impairing CD8 T cell proliferation and activation. Functionally, this suppression of CD8 T cell activity promoted malignant behaviors of HCC cells, including enhanced proliferation, reduced apoptosis, and increased angiogenesis. In vivo, accumulation of aged neutrophils accelerated HCC progression through CD8 T cell dysfunction, with minimal impact on distant metastasis. Mechanistically, HCC cell-derived high-mobility group box 1 (HMGB1) induced neutrophil senescence via activation of the Toll-like receptor 4 (TLR4) signaling pathway. Clinically, integrating circulating aged neutrophil with α-fetoprotein (AFP) substantially improved early HCC detection, while the CD8 T cell-to-aged neutrophil ratio demonstrated strong potential for malignant risk stratification. These findings identify HCC cell-derived HMGB1 as a driver of neutrophil senescence and reveal that aged neutrophils promote HCC progression by inducing CD8 T cell dysfunction through NET release. More importantly, aged neutrophils represent a robust noninvasive candidate marker for both HCC detection and assessment of malignant risk.
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5. {"_":"The PROM1SMAD5 Tumor-Initiating Subpopulation Shapes Premetastatic Niches through Spatial Multi-Omics Landscapes in HER2-Positive Breast Cancer.","sup":["+","+"]}
PMID:日期:2026-01-01Human epidermal growth factor receptor 2 (HER2)-positive breast cancer exhibits high metastatic potential, linked not only to intrinsic cancer cell traits but also to critical crosstalk with the tumor microenvironment. However, the coevolutionary mechanisms between cancer cells and multiple stromal subpopulations in driving distant metastasis remain poorly understood. Therefore, this study aimed to explore the microenvironmental regulatory mechanisms of breast tumor-initiating cells and their roles in HER2-positive breast cancer metastasis. Integrated multi-omics analyses (spatial transcriptomics, metabolomics, spatial in situ analysis, and proteomics) were used to identify novel cell subpopulations and their interactions. High-throughput sequencing of exosomal microRNAs (miRNAs) and single-nucleus RNA from the same tissue was performed to explore the molecular mechanisms underlying cell crosstalk. In vitro experiments were conducted to verify the interaction between stromal cells and prominin 1 (PROM1) SMAD family member 5 (SMAD5) cells. In vivo murine breast cancer models were established to confirm the role of stromal subpopulations in pulmonary metastasis, and parabiosis assays were carried out to compare key cell subpopulations between tumor-bearing mice and normal mice. Clinical samples were analyzed to correlate key cell subpopulations with clinicopathological features and prognosis. A breast tumor-initiating subpopulation, PROM1 SMAD5 cells, and its interactions with stromal cells, specifically adiponectin (ADIPOQ) notch receptor 4 (NOTCH4) adipocytes and decorin (DCN) transmembrane 4 L six family member 1 (TM4SF1) fibroblasts, were identified by integrated multi-omics analyses. Mechanistically, these 2 stromal subpopulations delivered functional miRNAs and mediated coatomer protein complex subunit alpha (COPA)-dependent epidermal growth factor receptor (EGFR) activation in PROM1SMAD5 cells, thereby triggering the EGFR-SMAD5-cytochrome P450 family 3 subfamily A member 4 (CYP3A4) axis to induce partial epithelial-mesenchymal transition (pEMT) and metastasis. Additionally, stroma-secreted exosomal miR-671-3p down-regulated Claudin1 in PROM1SMAD5 cells, promoting their evolution into PROM1SMAD5Claudin1 subpopulations with enhanced stemness and metastatic potential. In vivo experiments confirmed that the 2 stromal subpopulations markedly promoted pulmonary metastasis, and the 3 identified subpopulations preferentially accumulated in the primary tumors, lymph nodes, and pulmonary metastatic lesions of tumor-bearing mice. Clinically, these 3 subpopulations form a "trinity niche", whose aggregation associated with HER2 positivity, high malignancy, and lymph node/pulmonary metastasis, and predicted poor prognosis. This study clarified the microenvironmental regulation of breast tumor-initiating cells and provided new insights into precision therapy.
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6. Macrophages Drive Ferroptosis Resistance after Radiotherapy.
PMID:日期:2026-01-01Radiotherapy eliminates most tumor cells but spares persister tumor cells that evade cell death and drive relapse. Increasing evidence suggests that stromal components of the tumor microenvironment influence treatment responses, yet whether macrophages actively reprogram tumor-intrinsic stress responses to promote radioresistance remains unclear. Here, we investigated the mechanisms by which macrophage-tumor cell interactions regulate ferroptosis and tumor survival after irradiation. We used macrophage-tumor cell coculture systems, Transwell separation assays, and 3D microfluidic models to examine contact-dependent effects on tumor survival following irradiation. Kinome-wide small interfering RNA screening, RNA sequencing, lipidomic profiling, and quantitative proteomic analysis of secretomes were performed to identify signaling pathways and metabolic changes. Genetic and pharmacological perturbation of Ephrin receptor b4 (Ephb4) signaling were evaluated in vitro and in syngeneic mouse tumor models. Clinical relevance was assessed using transcriptomic analyses and immunohistochemical staining of patient tumor specimens. Macrophage contact reduced lipid peroxidation and cell death in irradiated tumor cells in a contact-dependent manner. Kinome screening identified Ephb4 as a key mediator induced by irradiation in tumor cells. Ephb4 engagement with ephrinb2 on macrophages initiated bidirectional signaling that increased expression of ferroptosis-protective genes (solute carrier family 7 member [], solute carrier family 3 member 2 [], and glutathione peroxidase 4 []) in tumor cells while activating the toll-like receptor 2- nuclear factor-kappa B pathway and interleukin-6 (IL-6) production in macrophages. Macrophage-derived IL-6 further sustained ferroptosis resistance in tumor cells, and Ephb4-driven secretion of cathepsin S amplified macrophage IL-6 production through a feedforward loop. Genetic or pharmacological inhibition of Ephb4 restored lipid peroxidation and markedly enhanced radiosensitivity in vitro and in vivo. Analysis of patient datasets demonstrated increased EPHB4 expression following radiotherapy and an association between high EPHB4 expression, reduced ferroptosis signatures, and poor treatment response. These findings identify a macrophage-driven ferroptosis evasion program that enables tumor cell survival after irradiation and demonstrate that Ephb4 coordinates bidirectional tumor-macrophage signaling to sustain this resistance. Targeting the Ephb4-ephrinb2 axis represents a potential strategy to enhance ferroptosis and improve radiotherapy efficacy in resistant tumors.
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7. Recruited Monocyte-Derived Macrophages Drive T Cell Inflammation in Immune Checkpoint Inhibitor-Mediated Pneumonitis.
7. 在免疫检查点抑制剂介导的肺炎中，招募的单核细胞衍生巨噬细胞驱动T细胞炎症PMID:日期:2026-01-01Immune checkpoint inhibitor-mediated pneumonitis (CIP) constitutes a major toxicity that limits the clinical application of cancer immunotherapy, whereas its underlying mechanisms remain incompletely understood. Current management relies on nonspecific immunosuppressants, lacking precision therapies. Although single-cell RNA sequencing (scRNA-seq) of bronchoalveolar lavage fluid (BALF) has implicated T cell activation and inflammatory myeloid responses in CIP pathogenesis, critical gaps persist regarding interstitial lung immunity and mechanisms governing monocyte/macrophage-T cell co-enrichment and crosstalk. We aimed to delineate the lung immune circuits that drive CIP and to identify targetable monocyte/macrophage-T cell pathways that could be leveraged for precision intervention. To elucidate CIP pathogenesis, we performed integrated scRNA-seq analysis of BALF from CIP and CIP patients with validation in a prospective cohort using flow cytometry, enzyme-linked immunosorbent assay, Western blotting, and quantitative polymerase chain reaction. Mechanistic studies were performed using an established tumor-bearing forkhead box P3-diphtheria toxin receptor-green fluorescent protein () mouse model of programmed death-1 inhibitor-induced CIP via micro-computed tomography, histopathology, scRNA-seq, flow cytometry, multiplex immunofluorescence, Western blotting, Transwell migration assays, and pharmacologic interventions. In CIP patient BALF and mouse lung tissues, CD8 T cells expressing cytotoxic effectors and C-X-C chemokine receptor 3 (CXCR3) expanded concomitantly with distinct C-C chemokine receptor 2 (CCR2) monocyte-derived macrophages (MoMΦ) exhibiting a highly inflammatory phenotype, while tissue-resident macrophages were markedly reduced. Mouse models revealed that expanded CCR2 MoMΦ originating from circulation replenished the depleted niche of lung-resident interstitial macrophages. Mechanistically, integrated in silico prediction and experimental validation demonstrated that CCR2 MoMΦ recruited CD8 T cells via the C-X-C motif chemokine ligand 9/10 (CXCL9/10)-CXCR3 axis. Conversely, CD8 T cells drove CCR2 MoMΦ expansion and pro-inflammatory phenotype via the interferon-γ (IFN-γ) axis, suggesting the existence of a positive feedback loop between these cell types. Pharmacological targeting of CCR2/CCR5 or CXCR3 signaling attenuated pneumonitis, reduced pulmonary CCR2 MoMΦ infiltration, diminished pathogenic T cell activation and cytotoxicity, and improved survival without compromising antitumor immunity. Our findings establish CCR2 MoMΦ and the IFN-γ-CXCL9/10-CXCR3 axis as core drivers of CIP pathogenesis and validate their therapeutic targeting potential. This work provides a scientific foundation for developing CIP-specific prevention and treatment strategies.
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8. {"_":"Metabolic Reprogramming of -Mediated mC Modification Promotes the Progression of Hepatocellular Carcinoma by Restricting Natural Killer Cell-Mediated Cytotoxicity.","i":["NSUN2"],"sup":["5"]}
8. {"_":"NSUN2介导的m5C修饰的代谢重编程通过限制自然杀伤细胞介导的细胞毒性促进肝细胞癌进展。","i":["NSUN2"],"sup":["5"]}PMID:日期:2026-01-01Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with resistance to immunotherapy posing a major clinical challenge. Natural killer (NK) cells exhibit impaired infiltration and cytotoxicity in HCC; however, the mechanisms underlying NK cell-mediated immune evasion are still poorly understood. This study investigated how NOP2/Sun RNA methyltransferase 2 (NSUN2), a 5-methylcytosine (mC) RNA methyltransferase, induces metabolic reprogramming and immunosuppression to drive HCC progression. We conducted a genome-wide CRISPR screen in HCC cells cocultured with NK cells. To delineate the downstream mechanisms, we integrated profiling of the m5C epitranscriptome, transcriptome, and chromatin landscape with metabolic characterization. The impact of on histone lactylation and programmed cell death 1 ligand 1 (PD-L1) transcription was further investigated. Functional assays in vitro and in vivo using syngeneic murine models and pharmacological inhibition validated these findings. Clinical relevance was assessed using patient tissues, The Cancer Genome Atlas dataset, and immunotherapy cohorts. Genome-wide CRISPR screening in HCC cell-NK cell coculture models identified as a key suppressor of NK cell-mediated cytotoxicity. Mechanistically, NSUN2-mediated RNA mC modification enhanced the messenger RNA stability and expression of glycolytic enzymes, including enolase 1 (), pyruvate kinase M1/2 (), and lactate dehydrogenase A (), thereby increasing lactate production. Accumulated lactate promoted histone H3 lysine 18 lactylation (H3K18la), which enhanced chromatin accessibility at the (encoding PD-L1) promoter and recruited signal transducer and activator of transcription 3 (STAT3) to drive PD-L1 expression, ultimately inhibiting NK cell-mediated cytotoxicity. Clinically, high NSUN2 expression was associated with elevated PD-L1 levels, poor prognosis, and immunotherapy resistance in patients with HCC. In vivo, knockout increased NK cell infiltration and suppressed tumor growth, while the STAT3 inhibitor TTI-101 combined with anti-PD-L1 therapy enhanced NK cell cytotoxicity and inhibited HCC progression. Our data demonstrated that NSUN2 drove immune evasion in HCC by coupling mC-dependent glycolytic reprogramming with H3K18la-mediated epigenetic activation of PD-L1. These findings suggest that NSUN2 could represent a critical nexus between mC RNA methylation and immunosuppression, providing a therapeutic rationale for combination immunotherapy in HCC.
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9. Targeting Epstein-Barr Virus for Cancer Vaccines: Recent Advances and Future Directions.
PMID:日期:2026-01-01该文献暂无摘要。