Cellular & Molecular Immunology细胞与分子免疫学
Cellular & Molecular Immunology(英文缩写 CELL MOL IMMUNOL),ISSN 1672-7681,eISSN 2042-0226,中文译名:细胞与分子免疫学 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
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 22.100 | Q1 |
| 2022 | 24.100 | Q1 |
| 2023 | 21.800 | Q1 |
| 2024 | 19.800 | Q1 |
| 2025 | 23.900 | Q1 |
Cellular & Molecular Immunology 最新收录文献
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1. αTIGIT-guided IL-15 mimetics drive potent and safe antitumor immunity by restoring tumor-infiltrating T cells.
PMID:日期:2026-09-11Cytokines are powerful modulators of antitumor immunity, but their clinical use is limited by structural instability, short half-life, poor drug-like properties, and severe systemic toxicity. Antibody-based cytokine mimetics have recently emerged to activate immune cells in vitro, but whether these mimetics can overcome the shortcomings of cytokines and exert therapeutic efficacy in vivo remains unclear. Here, we engineered bispecific antibody-based IL-15 mimetics using immunized Alpaca-derived phage display coupled with AlphaFold3-assisted structural screening and comparative screening of multiple formats to identify tandem IL-15 mimetics with strong in vitro bioactivity. Importantly, tandem IL-15R agonistic bispecifics, which simultaneously engage IL-15Rβ and γc, clearly demonstrated antitumor activity in vivo. To better target tumor-infiltrating lymphocytes (TILs), we incorporated a high-affinity anti-TIGIT antibody to guide tandem IL-15Rβγ agonists. This tri-antibody design, αTIGIT-αIL-15Rβγ, resulted in a striking improvement in antitumor activity without detectable systemic toxicity even at high doses. Mechanistically, αTIGIT-αIL-15Rβγ enhanced CD8⁺ T effector function and expanded the number of intratumoral stem-like T cells. Our study highlights a strategy to use TIL-targeted cytokine mimetics to overcome the limitations of native cytokines and enable dose pairing with immune checkpoint blockade (ICB), offering a path toward safer and more effective cytokine immunotherapy.
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2. HnRNPK restrains memory precursor and plasma cell differentiation to control germinal center B-cell output.
PMID:日期:2026-09-07Germinal center (GC) B cells are critical for the production of long-lived plasma cells and high-affinity antibodies. Upon exiting the GC reaction, B cells differentiate into either memory B (MB) cells or plasma cells depending on affinity signals and transcription factor profiles. However, the underlying transcriptional and metabolic mechanisms regulating this fate decision remain poorly understood. Here, we generated mice with B and GC B-cell-specific knockout of heterogeneous nuclear ribonucleoprotein K (hnRNPK). We found that hnRNPK deletion partially impaired B-cell development and, more strikingly, markedly attenuated the GC B-cell response. The reduction in GC B-cell numbers was attributed to excessive differentiation of precursor MB cells and plasma cells during the GC reaction. Mechanistically, hnRNPK directly suppressed the expression of the key MB cell-associated transcription factors Hhex and Zfp318. Moreover, we observed that compared with CD25-negative GC B cells, CD25-positive GC B cells displayed elevated glycolytic gene expression and significantly increased glucose uptake. HnRNPK deficiency further upregulated glycolytic activity, promoted CD25 expression, and consequently enhanced plasma cell differentiation. Blocking IL‑2/CD25 signaling mitigated the excessive plasmablast differentiation induced by hnRNPK loss and rescued the GC defects in hnRNPK‑deficient mice. Together, these findings demonstrate that hnRNPK controls GC B-cell output by transcriptionally repressing the expression of the MB cell-differentiation factors Hhex and Zfp318 and by modulating the glycolysis‑CD25 regulatory axis.
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3. p97-mediated proteostasis is a checkpoint for late-stage thymocyte positive selection.
PMID:日期:2026-09-07AAA ATPase p97 is a central regulator of protein homeostasis, yet its role in late-stage thymocyte development remains undefined. Here, we demonstrate that T-cell-specific ablation of p97 in mice severely blocks the double-positive (DP) to single-positive (SP) transition, with a pronounced defect in CD8 lineage commitment. Using both genetic deletion and acute pharmacological inhibition, we revealed a stage- and lineage-specific requirement for p97, with DP thymocytes being most sensitive to p97 loss. This failure in late-stage positive selection leads to intrathymic developmental arrest of immature DP cells and profound peripheral T-cell lymphopenia. Mechanistically, p97 deficiency results in the accumulation of ubiquitinated proteins, triggering the unfolded protein response and apoptosis in thymocytes. Furthermore, we identified a critical requirement for p97 in sustaining IL-7 receptor (IL-7R) expression and JAK signaling. Strikingly, pharmacological activation of JAK partially rescued SP thymocyte development in p97-deficient mice. Our findings establish p97-mediated protein homeostasis as a previously uncharacterized, cell-intrinsic checkpoint that is indispensable for late-stage positive selection by preventing proteostatic collapse and ensuring the fidelity of IL-7R signaling.
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4. Targeting the FOXP3-T-bet interaction to restore Treg stability in IFN-γ-driven autoimmunity.
4. 靶向FOXP3-T-bet相互作用以恢复IFN-γ驱动的自身免疫中Treg的稳定性PMID:日期:2026-09-03Regulatory T-cell (Treg) stability is maintained by dynamic remodeling of the FOXP3 transcriptional complex, and disruption of this complex leads to Treg dysfunction and immune dysregulation. However, how specific FOXP3 mutations alter the dynamic remodeling of the FOXP3 complex and thereby contribute to pathogenic Treg reprogramming in IPEX syndrome remains unclear. Here, we demonstrate that predominant Th1 inflammation manifests in both FOXP3 IPEX patients and FOXP3 knock-in mice and reveal that the mutation intrinsically impairs Treg-mediated control of Th1 inflammation, revealing a distinct pathogenesis of this mutation in IPEX syndrome. Mechanistically, the V408M mutation disrupts the FOXP3-T-bet interaction, impairing the FOXP3-mediated restraint of T-bet-driven IFN-γ production and thereby contributing to increased Th1 inflammation. Using an AI-driven virtual screening approach, we identified a first-in-class small molecule, FM029, that directly binds to FOXP3 and reinforces its interaction with T-bet. FM029 strongly suppressed Treg-derived IFN-γ production and alleviated IFN-γ-driven tissue inflammation in both FOXP3 mice and an acute colitis model. Collectively, these findings establish the FOXP3-T-bet interaction as a central checkpoint that governs Treg stability and IFN-γ-driven Th1 pathology, providing a proof-of-concept that pharmacologic stabilization of the FOXP3-T-bet interaction can mitigate IFN-γ-driven immune disorders.
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6. NADPH oxidases in immunometabolism and disease pathology: mechanistic networks, pollutant triggers, and therapeutic frontiers.
PMID:日期:2026-09-01NADPH oxidases (NOXs) have emerged as central hubs that link environmental, metabolic, and immune cues through spatially organized redox signaling. However, their roles across tissues and disease states have not been comprehensively evaluated in an integrated manner. This review integrates recent advances in structural biology, immunometabolism, toxicology, and systems biology to provide an updated, comprehensive, and accessible view of NOX biology. Recent advances in high‑resolution cryo-EM, AlphaFold‑based modeling and molecular dynamics studies have provided new insights into NOX architecture, catalytic sites, post‑translational modifications and regulatory mechanisms, and docking interfaces for RAC1 and p47. Emerging evidence further indicates that cellular NOX-derived ROS can reprogram macrophage and T-cell metabolism, stabilize HIF-1α, and tune the balance between effector and regulatory states, thereby linking NOX activity to checkpoint control and tumor immune escape. A second focus is on how real‑world pollutants converge on NOX isoforms as proximal mediators of redox signaling across lung, vascular, hepatic, renal, and neural tissues. NOX activation during cellular injury may contribute to oxidative stress, mitochondrial dysfunction, inflammasome activation, and fibrotic signaling, through extracellular vesicles, lipid rafts, and noncoding RNAs. Finally, the review evaluates emerging therapeutic strategies, including isoform-selective/pan-NOX/peptide inhibitors, and nanozymes. It also discusses emerging approaches such as exosome-based biomarkers, network pharmacology, and machine learning for patient stratification and pharmacodynamic monitoring. By highlighting key mechanistic gaps and translational opportunities, this review establishes NOXs as actionable nodal regulators at the intersection of immunity, metabolism, environmental exposure, and human disease.
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7. The FAM234A-USP4 axis governs T-cell fate through the dual regulation of mTOR and RORγt.
PMID:日期:2026-09-01该文献暂无摘要。
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8. {"_":"Radiation-induced CD200 tumor-associated macrophages suppress eosinophil-mediated antitumor immunity through CD200R signaling in hepatocellular carcinoma.","sup":["+"]}
8. 辐射诱导的CD200肿瘤相关巨噬细胞通过CD200R信号在肝细胞癌中抑制嗜酸性粒细胞介导的抗肿瘤免疫PMID:日期:2026-09-01Radiotherapy elicits dual immunomodulatory effects in cancer, activating antitumor immunity while paradoxically inducing immunosuppression, which limits therapeutic efficacy. The molecular pathways mediating postradiation immune escape in hepatocellular carcinoma (HCC) remain poorly defined. Here, we elucidate a previously uncharacterized mechanism whereby radiotherapy drives the accumulation of CD200 tumor-associated macrophages (TAMs) that suppress eosinophil-mediated antitumor immunity in patients with HCC. Through single-cell RNA sequencing of postradiotherapy HCC specimens, we demonstrated that radiation-induced DNA damage activated the cytosolic DNA-sensing STING pathway in TAMs, triggering NF-κB-dependent CD200 upregulation independent of canonical type I interferon signaling. These radiation-induced CD200 TAMs exhibited an immunosuppressive phenotype and correlated with adverse clinical outcomes in HCC patients. Mechanistically, CD200 TAMs established an immunosuppressive axis by recruiting CCR1 eosinophils through CCL3-mediated chemotaxis, subsequently inhibiting their antitumor functions via CD200-CD200R engagement. This interaction comprehensively suppressed NF-κB activation in eosinophils, impaired their antigen-presenting capacity and Th2 cytokine secretion and abrogated their ability to support CD8 T-cell-mediated cytotoxicity. Therapeutic blockade of CD200R following radiotherapy restored eosinophil effector functions, promoted central memory T-cell formation, and significantly enhanced tumor control across multiple preclinical HCC models. Remarkably, CD200R antagonism sensitized PD-1-refractory "cold" tumors to radioimmunotherapy combinations, overcoming primary resistance. Our findings establish STING-driven CD200 TAM accumulation and subsequent eosinophil dysfunction as critical determinants of radioresistance, positioning CD200R blockade as a promising therapeutic strategy to potentiate radioimmunotherapy responses in patients with HCC. Graphical abstract of the study findings. Radiotherapy-induced STING signaling activation promotes the accumulation of CD200 TAMs. These CD200 TAMs facilitate the recruitment of eosinophils via the CCL3-CCR1 chemotaxis axis while simultaneously suppressing eosinophil-mediated antitumor activity through CD200-CD200R engagement (left panel). Targeted blockade of CD200R following radiotherapy unleashed the antitumor potential of eosinophils, leading to enhanced infiltration and effector function of CTLs (right panel).
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9. NLRC3 enhances antitumor immunity by specifically negatively regulating M-MDSCs in a STING-dependent manner.
PMID:日期:2026-09-01NOD-like receptor (NLR) family CARD domain containing 3 (NLRC3), an intracellular member of the NLR family, is a negative regulator of both immune cell modulation and tumor cell proliferation. However, the role of NLRC3 and the mechanisms underlying its effect on the tumor immune microenvironment remain unclear. In this study, we report that NLRC3 promotes antitumor immunity by specifically negatively regulating the infiltration and immunosuppressive function of monocytic myeloid-derived suppressor cells (M-MDSCs). Mechanistically, NLRC3 inhibits the stimulator of interferon genes (STING) signaling pathway, leading to reduced expression of programmed cell death ligand 1 (PD-L1) and CCR2 in M-MDSCs, thereby limiting the infiltration and immunosuppressive function of M-MDSCs. Notably, overexpression of NLRC3 in combination with the STING agonist c-GAMP significantly inhibited tumor growth. These findings reveal a critical role for NLRC3 in modulating the immune microenvironment and provide insights into the optimization of NLRC3-targeted therapeutics.
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10. Tumor cell-released autophagosome (TRAP) programs inflammatory CAFs to drive the immune-excluded TIME through C3a.
PMID:日期:2026-09-01The immune-excluded tumor immune microenvironment (TIME) limits responses to ICIs. Cancer-associated fibroblasts are the most abundant stromal population and key regulators of immune suppression; however, the upstream cues that program pathogenic CAF states and the mechanisms of the immune-excluded TIME remain poorly defined. Here, by combining single-cell RNA sequencing and functional validation, we report that tumor cell-released autophagosome (TRAP) programs inflammatory CAFs (iCAFs) and triggers cathepsin L-dependent intracellular cleavage of C3 into C3a via the HSP70-TLR4-MyD88-ERK/p38 pathway. iCAF-derived C3a affects C3a on TAMs, promotes TAM accumulation in the iCAF-rich stroma, limits TIL trafficking into tumor nests, and reinforces an immune-excluded TIME. Disrupting the TRAP-iCAF-C3a/C3aR axis remodels the immune-excluded TIME and sensitizes tumors to anti-PD-L1 therapy. In clinical cohorts, plasma TRAP and C3a levels increased with disease stage, and their combination improved the discrimination of patients with breast cancer from controls (AUC = 0.96). These data define a TRAP-driven stromal-immune circuit that promotes immune exclusion and suggest that the C3a-C3aR axis is a potential target for enhancing ICI efficacy.