Cellular immunology最新文献

{"title":"The discovery of regulatory T cells: a paradigm shift in immunology","authors":"Simon Fillatreau ,&nbsp;Yi Hao","doi":"10.1016/j.cellimm.2025.105049","DOIUrl":"10.1016/j.cellimm.2025.105049","url":null,"abstract":"<div><div>The immune system is conventionally viewed as an army of fighters present naturally in an inactive state, ready to react to microbial invasion. Activation follows the detection of microbial molecules either by innate receptors, which are broadly expressed across cell types, or by antigen-specific receptors – the T cell receptor (TCR) and B cell receptor (BCR) - exclusively found on T and B lymphocytes, respectively. Previously to the discovery of regulatory T cells (Tregs), the induction of immune responses was thought to be controlled exclusively by the provision of activation signals coming from “outside” of the immune system. The discovery of regulatory T cells (Tregs) revealed a radically different mode of immune control. It emphasized immune activation as the default phenomenon at steady state, underlining suppression as essential to maintain immune homeostasis. Under this new view, the induction of immune response can proceed without external signal, upon the removal of key immune breaks internal to the immune system and embodied by Tregs. It fundamentally transformed our understanding of immune regulation and opened new therapeutic avenues for diseases ranging from autoimmunity to cancer. The immense impact of this work was rewarded this year by the attribution of the Nobel prize of Physiology and Medicine to Prof. Shimon Sakaguchi, Prof. Mary E. Brunkow, and Prof. Fred Ramsdell. In this article, we outline the scientific context of these discoveries in the 1990s, and discuss their impact for our understanding of the immune system and the development of novel therapies.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"419 ","pages":"Article 105049"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular immune response following homologous and heterologous BNT162b2 booster vaccination after primary immunization with BNT162b2 and CoronaVac respectively","authors":"Mat Jusoh Siti Asmaa ,&nbsp;Darren Shaqeel Sasikaran ,&nbsp;Aini Syahida Mat Yassim ,&nbsp;Bushra Solehah Mohd Rosdan ,&nbsp;Amiratul Aifa Mohamad Asri ,&nbsp;Anis Atifah Mohd Hisham ,&nbsp;Rapeah Suppian ,&nbsp;Nur Suhaila Idris ,&nbsp;Rosediani Muhamad ,&nbsp;Maryam Azlan ,&nbsp;Mohd Nor Norazmi","doi":"10.1016/j.cellimm.2026.105064","DOIUrl":"10.1016/j.cellimm.2026.105064","url":null,"abstract":"<div><div>Several vaccines targeting SARS-CoV-2 were developed following the COVID-19 outbreak. However, subsequent studies have indicated that humoral immune responses wane over time, particularly with the emergence of new SARS-CoV-2 variants. There is limited understanding of the resilience of T cell-mediated immunity induced by COVID-19 vaccines. This prospective cohort study involved a population who completed two primary doses of either the Pfizer BNT162b2 mRNA vaccine (PP) or the Sinovac Coronavac inactivated virus vaccine (SS) followed by one homologous (PPP) or heterologous (SSP) booster dose of BNT162b2, through convenience sampling of healthy adults. Blood samples were collected at three intervals, 2-weeks (T1), 6–8 months (T2), and 12-months (T3) following the booster immunization. Immunophenotyping was performed to evaluate T cell activity, memory, and intracellular cytokines at each timepoint. Our study found that the expression of T cell activation markers by both CD4+ and CD8+ T cells, such as CD25 + CD69+ and CD38 + HLA-DR+ was significantly higher at T2 compared to T1 in both PPP and SSP groups, indicating a robust T cell activation post-booster vaccination. Memory T cell subsets, including central memory and stem cell memory T cells, exhibited distinct kinetics, with both vaccines showing sustained levels of selected memory T cell subsets right up to about one year after booster. Furthermore, intracellular cytokine analysis revealed that CD4+ and CD8+ T cells in the SSP group exhibited higher level of IL-2, TNF-α and IFN-γ at specific timepoints, suggesting a stronger cellular immune response. These findings highlight the durability and qualitative differences in T cell-mediated immunity between homologous and heterologous vaccination regimens. While cellular immunity persisted in both groups up to 12 months post-booster, a decline in T3 underscores the potential, targeted need for additional booster doses to maintain protection against emerging SARS-CoV-2 variants.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"419 ","pages":"Article 105064"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TREM2 promotes susceptibility to colitis through the induction of gut microbiota dysbiosis","authors":"Jae-Eun Seo ,&nbsp;Jeong-Eun Seon ,&nbsp;Su-Min Yee ,&nbsp;Hyun-Su Koo ,&nbsp;Seo-Hee Moon ,&nbsp;Hae-Jin Seo ,&nbsp;Ja-Hun Seo ,&nbsp;Su-Man Kim ,&nbsp;Harim Choi ,&nbsp;Hyung-Sik Kang","doi":"10.1016/j.cellimm.2026.105062","DOIUrl":"10.1016/j.cellimm.2026.105062","url":null,"abstract":"<div><div>Triggering receptor expressed on myeloid cells 2 (TREM2) has been implicated in the pathogenesis of inflammatory bowel disease (IBD), yet its role in microbiota-mediated intestinal immune homeostasis remains incompletely defined. Here, we demonstrate that TREM2 expression is associated with exacerbated colonic inflammation in a murine model of DSS-induced colitis, disrupting epithelial integrity and microbial homeostasis. TREM2 transgenic (TG) mice developed more severe disease and mucosal injury, accompanied by marked dysbiosis characterized by the expansion of pro-inflammatory taxa (<em>Firmicutes, Actinobacteria, Prevotella</em>) and depletion of beneficial commensals (<em>Lactobacillus, Bifidobacterium</em>). This TREM2-driven dysbiotic and inflammatory state was associated with region-specific suppression of antimicrobial peptide (AMP) expression in the gut, elevated production of pro-inflammatory cytokines and reactive oxygen species (ROS), and a diminished frequency of IL-17A-producing Th17 cells in the colon. Conversely, TREM2 knockout (KO) mice preserved microbial composition, strengthened epithelial defenses, and attenuated inflammatory responses. Collectively, these findings establish TREM2 as a pivotal regulator of gut immune-microbial interactions and demonstrate its potential as a therapeutic target in IBD.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"419 ","pages":"Article 105062"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ibrutinib enhances stem-cell-memory T cell generation during early T cell activation but inhibits T cell proliferation","authors":"Ling He ,&nbsp;Yifei Liu ,&nbsp;Junjie Zhou ,&nbsp;Taiyan Zhang ,&nbsp;Shihao Zhang ,&nbsp;Jian Ge ,&nbsp;Jian Hong","doi":"10.1016/j.cellimm.2026.105065","DOIUrl":"10.1016/j.cellimm.2026.105065","url":null,"abstract":"<div><div>Ibrutinib has been demonstrated to restore T cell immunity of chronic lymphocytic leukemia patients, and enhance ex vivo expansion and function of CAR-T cells. In attempt to explore the effect of ibrutinib on unmanipulated T cells, we activated human PBMCs from healthy donors with CD3/CD28 stimulation and cultured them with or without ibrutinib under various conditions. Phenotypic and functional assessments were then performed using flow cytometry. Results showed that ibrutinib could downregulate programmed cell death protein 1 expression and reduce activation-induced cell death of T cells. Additionally, ibrutinib added at the onset of T cell activation, rather than 48 h later, could further promote the generation of CD45RA⁺CCR7⁺CD95⁺ stem-cell-memory T cell subset in the presence of IL-7 and IL-15. However, ibrutinib also suppressed the proliferation and cytokine-secretion capacity of T cells in a dose-dependent manner. Further RNA sequencing of activated CD8⁺ T cells demonstrated that ibrutinib administration at the onset of T cell activation modulated multiple TCR downstream signaling pathways, notably downregulating mTORC1 signaling and upregulating FOXO1 signaling. In contrast, ibrutinib added 48 h post-activation did not show these effects. These findings suggest that caution should be exercised when incorporating ibrutinib into ex vivo expansion system for adoptive non-genetically engineered T cells or combining ibrutinib with these T cell immunotherapies in clinical trial settings.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"419 ","pages":"Article 105065"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BCG and β-glucan primed monocytes yield dendritic cells that hamper the induction of pro-inflammatory T cell immunity","authors":"Jorge Cuenca-Escalona ,&nbsp;Robbin Kramer ,&nbsp;Clara Marjalizo-Jimenez ,&nbsp;Jorge Domínguez-Andrés ,&nbsp;Mihai G. Netea ,&nbsp;Georgina Flórez-Grau ,&nbsp;I. Jolanda M. de Vries ,&nbsp;Sophie K. Horrevorts","doi":"10.1016/j.cellimm.2025.105060","DOIUrl":"10.1016/j.cellimm.2025.105060","url":null,"abstract":"<div><div>Dendritic cells (DCs) are professional antigen-presenting cells that regulate inflammatory and tolerogenic immunity. Their role within trained immunity, a process in which innate immune cells exhibit memory-like characteristics, remains to be elucidated. To date, increasing evidence indicates that trained immunity underlies the enhanced innate immune response induced by the Bacillus Calmette-Guérin (BCG) vaccine and the fungal cell wall component β-glucan (β-Glc), contributing to protection against heterologous infections and cancer. Concurrently, preclinical evidence suggests that BCG can also attenuate the severity of autoimmunity. Given the unclear immunomodulatory effects of these compounds on DCs we investigated the effects of BCG and β-Glc on human monocyte-derived DCs (moDCs).</div><div>Our results demonstrate that early exposure to BCG and β-Glc during moDC development steers their function towards tolerance, indicated by reduced pro-inflammatory cytokine production upon rechallenge. Additionally, BCG and β-Glc challenge hampered the moDCs' ability to mount proinflammatory IFN-γ-driven T cell responses, while mediating the enrichment of regulatory T cells. Metabolically, we potentially observe signs that BCG amplifies glycolysis but not oxidative phosphorylation. Together, our findings provide novel insights into the role of BCG and β-Glc on human DCs and support the therapeutic potential of modulating human DCs with these training agents for the treatment of autoimmune disorders.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"419 ","pages":"Article 105060"},"PeriodicalIF":2.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145904125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stromal cells relieved systemic lupus erythematosus via CCL2 dependent macrophage polarization","authors":"Xin Wen ,&nbsp;Genhong Yao ,&nbsp;Yujie Zhou ,&nbsp;Shanshan Liu ,&nbsp;Lingyun Sun","doi":"10.1016/j.cellimm.2025.105046","DOIUrl":"10.1016/j.cellimm.2025.105046","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) was an autoimmune disease leading to high morbidity and mortality without effective and low-side effect conventional drugs. Our previous clinical studies demonstrated umbilical cord derived mesenchymal stromal cells (MSCs) were a safe and effective treatment, but its therapeutic mechanism is still unclear. In this study, we first observed clinical used MSCs exhibited higher CCL2 expression than primary and aged MSCs, and abnormal bone marrow derived MSC (BM-MSC) from SLE patients performed decreased CCL2 expression compared to healthy control. Then, we constructed CCL2-deficient MSCs, and found the immunosuppressive activity of CCL2-deficient MSCs was impaired in the peripheral blood mononuclear cell (PBMC) inhibitory assay <em>in vitro</em>. CCL2-deficient MSCs also failed to relieve SLE in MRL/lpr and pristine-induced mice. To further explore the role of CCL2 in MSC therapy, we performed transcriptomic profiling of CCL2-deficient MSCs and MSCs, and identified the differential expressed genes were related to chemotaxis, including monocyte chemotaxis. Subsequently, we found that MSCs restored the imbalance in M1/M2 macrophage polarization <em>via</em> CCL2 <em>in vitro</em>. These findings provided valuable insight for investigating the therapeutic mechanism of MSC on SLE.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"418 ","pages":"Article 105046"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the impact of using bone marrow-derived macrophages to turn early tumor sites into hot early tumor sites","authors":"Joshua Finn,&nbsp;Emily Kessler,&nbsp;Melissa Lass,&nbsp;Ernesto Oviedo-Bermudez,&nbsp;Robert A. Kurt","doi":"10.1016/j.cellimm.2025.105050","DOIUrl":"10.1016/j.cellimm.2025.105050","url":null,"abstract":"<div><div>The impact of transforming an early tumor site into a hot early tumor site was evaluated using bone marrow-derived macrophages (BMDM) activated with IFN-γ and sCD40L in combination with Toll-like receptor (TLR) agonists (lipopolysaccharide (LPS), flagellin or R848). Not surprisingly, analysis of the activated BMDM revealed characteristics often ascribed to anti-tumor (M1) macrophages with production of nitrite and IL-12, as well as expression of <em>Il-1b</em>, <em>Il-6</em>, <em>Tnf-a</em>, <em>Il-18</em>, <em>Ccl5</em>, <em>Cxcl9</em>, <em>Cxcl10</em>, and <em>Cxcl11</em>. All treatments also led to a significant increase in MHC Class II or CD80 expression, but only BMDM activated with IFN-γ and LPS showed a significant increase in both MHC Class II and CD80 expression. Delivering these BMDM to early tumor sites slowed progression of three murine mammary carcinoma models (EMT6, 168, 4 T1). Depletion studies revealed that the anti-tumor activity was dependent upon CD8⁺ T cells and NK cells suggesting that expression of <em>Ccl5</em>, <em>Cxcl9</em>, <em>Cxcl10</em>, and/or <em>Cxcl11</em> may be important for the <em>in vivo</em> function of the BMDM. Additionally, inhibiting G protein coupled receptor (GPCR) signaling in the BMDM ablated the anti-tumor activity suggesting that the anti-tumor activity may be dependent on the migratory ability of the BMDM. Collectively, these data show that creating hot early tumor sites by delivering anti-tumor BMDM can impact tumor growth by eliciting CD8⁺ T cells and NK cells, and that BMDM anti-tumor activity depends on GPCR-mediated signaling.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"418 ","pages":"Article 105050"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145502475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cgas deficiency promotes tumor growth by supporting B cell persistence and angiogenesis","authors":"Papasara Chantawichitwong ,&nbsp;Sarinya Kumpunya ,&nbsp;Tossapon Wongtangprasert ,&nbsp;Peerapat Visitchanakun ,&nbsp;Trairak Pisitkun ,&nbsp;Prapaporn Pisitkun","doi":"10.1016/j.cellimm.2025.105036","DOIUrl":"10.1016/j.cellimm.2025.105036","url":null,"abstract":"<div><div>The cGAS sensor activates the STING/IFN signaling pathway, which is crucial for antiviral and antitumor responses. This study aims to investigate the cGAS-mediated immune responses in tumorigenesis using the MC-38 tumor model. MC38-tumor models were established in wild-type (WT) and <em>Cgas</em>-deficient mice to investigate immunophenotypes and cellular mechanisms involved in tumor progression. <em>Cgas</em>^{<em>−/−</em>} mice exhibited significantly larger tumors and reduced survival compared to WT mice. Tumors in <em>Cgas</em>^{<em>−/−</em>} mice showed increased fibrosis and neovascularity. WT mice mounted a more robust T-cell-mediated antitumor response, with higher levels of NK and effector T cells, while <em>Cgas</em>^{<em>−/−</em>} mice showed an expansion of B cells, including regulatory B cells producing IL-10. B cells from tumor-bearing <em>Cgas</em>^{<em>−/−</em>} mice demonstrated enhanced survival in the tumor-conditioned medium than those from WT mice. B cell depletion significantly reduced tumor size in WT mice but had minimal effect in <em>Cgas</em>^{<em>−/−</em>} mice, where fibrosis and tumor vasculature persisted. Notably, despite B cell depletion, B cells remained in the tumors of <em>Cgas</em>^{<em>−/−</em>} mice, in contrast to WT mice, where depletion correlated with increased CD8⁺ T cell infiltration. Upregulation of <em>Tgfb1</em>, <em>Tlr7</em>, <em>Tlr9</em>, and <em>Tnfrsf13c</em> in tumors of <em>Cgas</em>^{<em>−/−</em>} mice suggested a tumor microenvironment (TME) that promotes B cell survival. Furthermore, <em>Cgas</em>^{<em>−/−</em>} B cells promoted angiogenesis, as indicated by enhanced endothelial tube formation. cGAS deficiency fosters tumor growth by reducing the antitumor response, promoting a pro-tumor microenvironment, and supporting B cell survival. The <em>Cgas</em>^{<em>−/−</em>} B cells enhance angiogenesis and are resistant to B cell depletion, contributing to tumor progression.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"418 ","pages":"Article 105036"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EGCG remodels the TGF-β cervical cancer micro-environment towards immune responsiveness","authors":"Jayapradha Gnanagurusamy ,&nbsp;Rajalakshmi Sabanayagam ,&nbsp;Sneha Krishnamoorthy ,&nbsp;Vidya Balasubramanian ,&nbsp;Sridhar Muthusami","doi":"10.1016/j.cellimm.2025.105027","DOIUrl":"10.1016/j.cellimm.2025.105027","url":null,"abstract":"<div><h3>Background</h3><div>Exploring the role of immune modulators alongside TGF-β in cervical cancer (CC) and PBMCs may improve the understanding of targeted treatment strategies.</div></div><div><h3>Methods</h3><div>We analyzed expression, overall survival (OS), correlation and tumor infiltration of PD-L1, CD55 and CD46, as well as immune cell fractions in CC patients using OncoDB, TIMER 2.0 and TCIA. RT-PCR and western blotting was performed to assess PD-L1, CD55 and CD46 expression. Viability, mitored, apoptosis and MMP-2 were evaluated in CC cells co-cultured with PBMCs. Morphology, crystal violet staining, ROS and MMP-2 were examined in SiHa spheroids.</div></div><div><h3>Results</h3><div>PD-L1 was upregulated, CD55 was significantly increased and CD46 showed no significant difference in HPV16 positive compared with HPV negative individuals. Elevated PD-L1, CD55 and CD46 were associated with reduced OS in HPV16 positive individuals. PD-L1 and CD55 showed moderate positive and negative correlation with TGF-β, respectively, whereas CD46 correlation was negligible. Immune fractions including M1 macrophages (31 %), M2 macrophages (17 %), CD8 T cells (21 %), NK cells (10 %), were linked to reduced OS. TGF-β, PD-L1 and CD46 infiltration were positively corelated with CD8+ T cells. In CC cells, TGF-β stimulation increased PD-L1, while decreasing CD55 and CD46, reducing viability, metabolic activity and inducing apoptosis in HPV (+) co-cultures. EGCG treatment under TGF-β, reduced PD-L1, CD55 and CD46 expression, decreased viability, metabolic activity and MMP-2 secretion, while inducing apoptosis in SiHa co-culture. In 3D spheroids, EGCG inhibited proliferation and MMP-2 activity while increasing ROS production.</div></div><div><h3>Conclusion</h3><div>EGCG, by targeting TGF-β and modulating PD-L1 and mCRPs, represents a promising candidate for immunotherapeutic development in CC.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"418 ","pages":"Article 105027"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145128348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophages: Traffic centers in the tumor immune microenvironment","authors":"Fan Zou,&nbsp;Yishan Zhang,&nbsp;Mingdong Wang,&nbsp;Yongjun Quan,&nbsp;Hao Ping","doi":"10.1016/j.cellimm.2025.105037","DOIUrl":"10.1016/j.cellimm.2025.105037","url":null,"abstract":"<div><div>The tumor microenvironment (TME) has emerged as a prominent focus of cancer research in recent years, with various drugs in this field, including programmed cell death receptor 1 (PD-1) antibodies and cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies, now included in first-line therapeutic guidelines for cancer. Although macrophages are not as effective as T-lymphocytes in directly killing tumors, they serve as critical mediators in the TME due to their indirect roles in promoting blood vessel formation, facilitating antigen presentation and influencing tumor cell metabolism to affect their infiltration. Macrophages are governed by complex regulatory networks, both independently and as a part of the TME. Extensive research has led to the development of a comprehensive and detailed understanding of these networks and the molecular mechanisms driving macrophage activity. The interactions between macrophages and the TME significantly impact tumor initiation and progression, making macrophages a promising target for cancer therapy. In this review, we discuss recent findings on the factors underlying macrophage polarization in the TME, the critical role of macrophages within the TME, key transcriptional regulators of macrophages, and emerging strategies for targeting macrophages in cancer therapy.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"418 ","pages":"Article 105037"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145264055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}