Pub Date : 2026-01-21DOI: 10.1016/j.clim.2026.110665
Afshin Derakhshani , Roberta Di Fonte , Letizia Porcelli , Fatemeh Nejadi Orang , Mahdi Abdoli Shadbad , Adib Miraki Feriz , Hossein Safarpour , Antoine Dufour , Behzad Baradaran , Angela Calabrese , Mario Testini , Riccardo Memeo , Giovanna Di Meo , Leonardo Vincenti , Sonali Bhardwaj , Vito Racanelli , Nicola Silvestris , Oronzo Brunetti , Amalia Azzariti
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal malignancies, underscoring the need for minimally invasive biomarkers to support patient stratification and disease monitoring. In this study, we aimed to identify PDAC-associated immune signatures by reanalyzing a single-cell RNA-sequencing dataset and to validate key findings using flow cytometry in an independent cohort predominantly composed of advanced-stage PDAC. Analysis of peripheral blood mononuclear cells from patients with PDAC and healthy donors revealed increased expression of S100A6, S100A8, and S100A12, particularly within monocytes and dendritic cells. These transcriptional changes were confirmed at the protein level, demonstrating enrichment of S100A6+ monocytes, S100A6+/S100A8+ DCs, activated monocytes, and plasmacytoid DCs in PDAC. Univariate ROC analyses identified S100A6+ plasmacytoid DCs, S100A8+ plasmacytoid DCs, and CD14+CD86+S100A8+ monocytes as candidate PDAC-associated immune features. However, further validation incorporating benign pancreatic conditions and multivariable modeling is required before conclusions can be drawn regarding diagnostic specificity and clinical applicability.
{"title":"Integrated single cell RNA sequencing and flow cytometry analysis identifies elevated S100A6+ and S100A8+ myeloid subsets in pancreatic ductal adenocarcinoma","authors":"Afshin Derakhshani , Roberta Di Fonte , Letizia Porcelli , Fatemeh Nejadi Orang , Mahdi Abdoli Shadbad , Adib Miraki Feriz , Hossein Safarpour , Antoine Dufour , Behzad Baradaran , Angela Calabrese , Mario Testini , Riccardo Memeo , Giovanna Di Meo , Leonardo Vincenti , Sonali Bhardwaj , Vito Racanelli , Nicola Silvestris , Oronzo Brunetti , Amalia Azzariti","doi":"10.1016/j.clim.2026.110665","DOIUrl":"10.1016/j.clim.2026.110665","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal malignancies, underscoring the need for minimally invasive biomarkers to support patient stratification and disease monitoring. In this study, we aimed to identify PDAC-associated immune signatures by reanalyzing a single-cell RNA-sequencing dataset and to validate key findings using flow cytometry in an independent cohort predominantly composed of advanced-stage PDAC. Analysis of peripheral blood mononuclear cells from patients with PDAC and healthy donors revealed increased expression of S100A6, S100A8, and S100A12, particularly within monocytes and dendritic cells. These transcriptional changes were confirmed at the protein level, demonstrating enrichment of S100A6<sup>+</sup> monocytes, S100A6<sup>+</sup>/S100A8<sup>+</sup> DCs, activated monocytes, and plasmacytoid DCs in PDAC. Univariate ROC analyses identified S100A6<sup>+</sup> plasmacytoid DCs, S100A8<sup>+</sup> plasmacytoid DCs, and CD14<sup>+</sup>CD86<sup>+</sup>S100A8<sup>+</sup> monocytes as candidate PDAC-associated immune features. However, further validation incorporating benign pancreatic conditions and multivariable modeling is required before conclusions can be drawn regarding diagnostic specificity and clinical applicability.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"284 ","pages":"Article 110665"},"PeriodicalIF":3.8,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-19DOI: 10.1016/j.clim.2026.110667
Jinkai Liang , Jiaqi Wang , Hui Fang , Xin Tang, Ke Xue, Wanting Liu, Shuai Shao, Gang Wang
Neutrophils are key components of the innate immune system, rapidly migrating to sites of infection or inflammation to perform bactericidal functions. Their lifespan is short, spanning from development and circulation to migration, aging, and eventual death. Neutrophil death plays a critical role in both physiological and pathological processes. This review explores the different death mechanisms of neutrophils, including apoptosis, NETosis, pyroptosis, necroptosis, and ferroptosis, and discusses their implications in immune-mediated inflammatory diseases (IMIDs). This review examines the connection between neutrophil metabolism and cell death, as well as potential interactions among these death pathways. A clearer understanding of these death mechanisms in the context of immune diseases can enhance our comprehension of disease pathogenesis and inform the development of targeted therapeutic strategies.
{"title":"Life towards death: Neutrophils in immune-mediated inflammatory diseases","authors":"Jinkai Liang , Jiaqi Wang , Hui Fang , Xin Tang, Ke Xue, Wanting Liu, Shuai Shao, Gang Wang","doi":"10.1016/j.clim.2026.110667","DOIUrl":"10.1016/j.clim.2026.110667","url":null,"abstract":"<div><div>Neutrophils are key components of the innate immune system, rapidly migrating to sites of infection or inflammation to perform bactericidal functions. Their lifespan is short, spanning from development and circulation to migration, aging, and eventual death. Neutrophil death plays a critical role in both physiological and pathological processes. This review explores the different death mechanisms of neutrophils, including apoptosis, NETosis, pyroptosis, necroptosis, and ferroptosis, and discusses their implications in immune-mediated inflammatory diseases (IMIDs). This review examines the connection between neutrophil metabolism and cell death, as well as potential interactions among these death pathways. A clearer understanding of these death mechanisms in the context of immune diseases can enhance our comprehension of disease pathogenesis and inform the development of targeted therapeutic strategies.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"284 ","pages":"Article 110667"},"PeriodicalIF":3.8,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-19DOI: 10.1016/j.clim.2026.110664
Yiyang Wu , Jintian Wang , Pengcheng Wang , Qiwei Chen , Jing Jia , Yan Liu , Yao Chen , Kai Ye
Background
Microsatellite-stable colorectal cancer (MSS CRC) resists immune checkpoint inhibitors. FGF19's immunomodulatory role in MSS CRC remains unclear.
Methods
Bioinformatics analyzed FGF19 expression and CD8+ T-cell infiltration. CRC cells co-cultured with neutrophils (dHL-60) assessed chemotaxis and NET markers. LDH assay, ELISA, and CFSE staining measured CD8+ T-cell activity. CCK-8, EdU, Transwell, and flow cytometry assessed CRC phenotypes. Mouse model tested PD-1 antibody and FGFR4 inhibitor BLU-9931.
Results
FGF19 was upregulated in non-immunogenic MSS CRC, negatively correlating with CD8+ T cells. Elevated FGF19 enhanced neutrophil chemotaxis and NET release, inhibiting CD8+ T-cell cytotoxicity and proliferation while promoting malignant CRC behavior. Mechanistically, FGF19-FGFR4 signaling was associated with increased ERK pathway activity, elevated IL-8 levels, and NET formation. Blocking FGF19-FGFR4 enhanced PD-1 efficacy in MSS CRC.
Conclusion
The FGF19/ERK/IL-8 pathway contributed to NET formation in this model. Targeting this pathway represents a promising strategy to boost immunotherapy in MSS CRC.
{"title":"Inhibition of neutrophil extracellular traps via the FGF19/ERK/IL-8 axis enhances immune therapy in MSS colorectal cancer","authors":"Yiyang Wu , Jintian Wang , Pengcheng Wang , Qiwei Chen , Jing Jia , Yan Liu , Yao Chen , Kai Ye","doi":"10.1016/j.clim.2026.110664","DOIUrl":"10.1016/j.clim.2026.110664","url":null,"abstract":"<div><h3>Background</h3><div>Microsatellite-stable colorectal cancer (MSS CRC) resists immune checkpoint inhibitors. FGF19's immunomodulatory role in MSS CRC remains unclear.</div></div><div><h3>Methods</h3><div>Bioinformatics analyzed FGF19 expression and CD8<sup>+</sup> T-cell infiltration. CRC cells co-cultured with neutrophils (dHL-60) assessed chemotaxis and NET markers. LDH assay, ELISA, and CFSE staining measured CD8<sup>+</sup> T-cell activity. CCK-8, EdU, Transwell, and flow cytometry assessed CRC phenotypes. Mouse model tested PD-1 antibody and FGFR4 inhibitor BLU-9931.</div></div><div><h3>Results</h3><div>FGF19 was upregulated in non-immunogenic MSS CRC, negatively correlating with CD8<sup>+</sup> T cells. Elevated FGF19 enhanced neutrophil chemotaxis and NET release, inhibiting CD8<sup>+</sup> T-cell cytotoxicity and proliferation while promoting malignant CRC behavior. Mechanistically, FGF19-FGFR4 signaling was associated with increased ERK pathway activity, elevated IL-8 levels, and NET formation. Blocking FGF19-FGFR4 enhanced PD-1 efficacy in MSS CRC.</div></div><div><h3>Conclusion</h3><div>The FGF19/ERK/IL-8 pathway contributed to NET formation in this model. Targeting this pathway represents a promising strategy to boost immunotherapy in MSS CRC.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"284 ","pages":"Article 110664"},"PeriodicalIF":3.8,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-19DOI: 10.1016/j.clim.2026.110666
Ting Feng , Chaying He , Yanhua Ding, Wei Huang, Yinghua Li
Incomplete abortion is a common complication of medical abortion, potentially related to immune dysregulation. The roles of dendritic cells, Th1/Th2 polarization, and formyl peptide receptor 3 (FPR3) in abortion outcomes are not well understood. We retrospectively analyzed 175 women who underwent early medical abortion between January 2022 and March 2025, classifying them into complete (CA) and incomplete abortion (ICA) groups. A murine model was also used, with mifepristone administered on embryonic days 6.5 to 8.5. FPR3 expression was significantly lower in ICA tissues compared to CA. CA samples showed higher Th1 marker levels and lower Th2 marker levels (all P < 0.001). In mice, mifepristone increased Fpr3 and Tbx21 mRNA levels by 3.5- and 4-fold, respectively, and decreased Gata3 expression by ∼55%. Protein analysis showed similar trends. Mifepristone treatment was accompanied by upregulation of FPR3 and a Th1-biased/Th2-suppressed molecular profile, suggesting a previously unrecognized immune-mediated mechanism that may complement its endocrine effects.
{"title":"Relationship between Th1/Th2 balance and medical abortion outcomes in early medical abortion patients","authors":"Ting Feng , Chaying He , Yanhua Ding, Wei Huang, Yinghua Li","doi":"10.1016/j.clim.2026.110666","DOIUrl":"10.1016/j.clim.2026.110666","url":null,"abstract":"<div><div>Incomplete abortion is a common complication of medical abortion, potentially related to immune dysregulation. The roles of dendritic cells, Th1/Th2 polarization, and formyl peptide receptor 3 (FPR3) in abortion outcomes are not well understood. We retrospectively analyzed 175 women who underwent early medical abortion between January 2022 and March 2025, classifying them into complete (CA) and incomplete abortion (ICA) groups. A murine model was also used, with mifepristone administered on embryonic days 6.5 to 8.5. FPR3 expression was significantly lower in ICA tissues compared to CA. CA samples showed higher Th1 marker levels and lower Th2 marker levels (all <em>P</em> < 0.001). In mice, mifepristone increased Fpr3 and Tbx21 mRNA levels by 3.5- and 4-fold, respectively, and decreased Gata3 expression by ∼55%. Protein analysis showed similar trends. Mifepristone treatment was accompanied by upregulation of FPR3 and a Th1-biased/Th2-suppressed molecular profile, suggesting a previously unrecognized immune-mediated mechanism that may complement its endocrine effects.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"284 ","pages":"Article 110666"},"PeriodicalIF":3.8,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-14DOI: 10.1016/j.clim.2026.110663
Chih-Chun Lee , Li-Chung Chiu , Shih-Ching Lee , Tien-Ming Chan
Objective
Dermatomyositis (DM), a subset of idiopathic inflammatory myopathies, affects the skin and skeletal muscles and is associated with an increased cancer risk, particularly in patients with antibodies against transcriptional intermediary factor 1γ (TIF1γ). This study aimed to evaluate the diagnostic value of anti–TIF1γ antibodies and assess their clinical significance, especially regarding cancer risk and associations with other autoimmune diseases (including overlap syndromes).
Methods
In this multicenter retrospective study, we identified patients with positive anti–TIF1γ tests from Chang Gung Medical Foundation (2019–2021). Anti–TIF1γ and anti–Ro52 antibodies were detected via line blot and fluorescent enzyme immunoassay. Patients were stratified into strong-positive (++/+++) versus weak-positive (+) groups and analyzed for clinical features and cancer prevalence. Data spanned three full years and were statistically evaluated.
Results
Among 84 patients with anti–TIF1γ antibody positivity, 19 (22.6%) were diagnosed with DM, including 15 patients in the strong-positive group and 4 patients in the weak-positive group, and 8 (9.5%) developed malignancy. Strong anti–TIF1γ positivity was significantly linked to dermatomyositis (46.7% vs. 7.4% in weak-positive, p < 0.05) and higher cancer incidence (20.0% vs. 3.7%, p = 0.0221). Moreover, concurrent anti–TIF1γ and anti–Ro52 seropositivity correlated with systemic lupus erythematosus (23.8% vs. 4.8%, p = 0.0211) and SLE–SjS overlap (14.3% vs. 0%, p = 0.0140). Typical skin findings included heliotrope rash, Gottron sign, and periungual telangiectasias; malignancies observed were nasopharyngeal carcinoma and lung cancer in this cohort.
Conclusions
High anti-TIF1γ titers significantly increase dermatomyositis and cancer risk. Concomitant anti-Ro52 was associated with SLE and SLE–SjS overlap, emphasizing the necessity of comprehensive myositis antibody profiling for diagnosis and risk assessment.
{"title":"Clinical prognosis and cancer risk assessment in autoimmune diseases with anti–TIF1γ alone or concurrent with anti–Ro52 antibodies in a Taiwanese cohort","authors":"Chih-Chun Lee , Li-Chung Chiu , Shih-Ching Lee , Tien-Ming Chan","doi":"10.1016/j.clim.2026.110663","DOIUrl":"10.1016/j.clim.2026.110663","url":null,"abstract":"<div><h3>Objective</h3><div>Dermatomyositis (DM), a subset of idiopathic inflammatory myopathies, affects the skin and skeletal muscles and is associated with an increased cancer risk, particularly in patients with antibodies against transcriptional intermediary factor 1γ (TIF1γ). This study aimed to evaluate the diagnostic value of anti–TIF1γ antibodies and assess their clinical significance, especially regarding cancer risk and associations with other autoimmune diseases (including overlap syndromes).</div></div><div><h3>Methods</h3><div>In this multicenter retrospective study, we identified patients with positive anti–TIF1γ tests from Chang Gung Medical Foundation (2019–2021). Anti–TIF1γ and anti–Ro52 antibodies were detected via line blot and fluorescent enzyme immunoassay. Patients were stratified into strong-positive (++/+++) versus weak-positive (+) groups and analyzed for clinical features and cancer prevalence. Data spanned three full years and were statistically evaluated.</div></div><div><h3>Results</h3><div>Among 84 patients with anti–TIF1γ antibody positivity, 19 (22.6%) were diagnosed with DM, including 15 patients in the strong-positive group and 4 patients in the weak-positive group, and 8 (9.5%) developed malignancy. Strong anti–TIF1γ positivity was significantly linked to dermatomyositis (46.7% vs. 7.4% in weak-positive, <em>p</em> < 0.05) and higher cancer incidence (20.0% vs. 3.7%, <em>p</em> = 0.0221). Moreover, concurrent anti–TIF1γ and anti–Ro52 seropositivity correlated with systemic lupus erythematosus (23.8% vs. 4.8%, <em>p</em> = 0.0211) and SLE–SjS overlap (14.3% vs. 0%, <em>p</em> = 0.0140). Typical skin findings included heliotrope rash, Gottron sign, and periungual telangiectasias; malignancies observed were nasopharyngeal carcinoma and lung cancer in this cohort.</div></div><div><h3>Conclusions</h3><div>High anti-TIF1γ titers significantly increase dermatomyositis and cancer risk. Concomitant anti-Ro52 was associated with SLE and SLE–SjS overlap, emphasizing the necessity of comprehensive myositis antibody profiling for diagnosis and risk assessment.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110663"},"PeriodicalIF":3.8,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recent advances in NSCLC therapy remain limited by treatment resistance, much of which is influenced by epigenetic regulation of immune responses. In this study, we investigate the role of CTCF, a chromatin architectural protein that modulates enhancer–promoter interactions, in shaping T-helper (TH) cell differentiation and tumor immunity. Changes in CTCF expression coincided with altered chromatin-level enrichment patterns involving DNA repair–associated factors (ERCC1, XPF, CSA) and tumor-related proteins at the IFNG locus, as well as shifts in histone modification marks (H3K4me3 and H3K27me3) at TH1-associated genes, including TBX21 and IFNG. These chromatin-associated features were accompanied by increased nitric oxide production and enhanced cytotoxicity in functional assays. Collectively, these findings suggest that variation in CTCF levels is linked to coordinated epigenetic and immune-associated changes in NSCLC, supporting its potential relevance as an immuno-epigenetic factor in shaping anti-tumor immune responses.
{"title":"Involvement of CCCTC-binding factor (CTCF) in immunomodulation and epigenetic regulation of T helper cell differentiation during Non-Small Cell Lung Cancer (NSCLC)","authors":"Oishi Mukherjee , Sayani Bose , Sudeshna Rakshit , Geetha Shanmugam , Anuneha Baranwal , Srawsta Saha , Harsita Goswami , Melvin George , Koustav Sarkar","doi":"10.1016/j.clim.2025.110662","DOIUrl":"10.1016/j.clim.2025.110662","url":null,"abstract":"<div><div>Recent advances in NSCLC therapy remain limited by treatment resistance, much of which is influenced by epigenetic regulation of immune responses. In this study, we investigate the role of CTCF, a chromatin architectural protein that modulates enhancer–promoter interactions, in shaping T-helper (T<sub>H</sub>) cell differentiation and tumor immunity. Changes in CTCF expression coincided with altered chromatin-level enrichment patterns involving DNA repair–associated factors (ERCC1, XPF, CSA) and tumor-related proteins at the <em>IFNG</em> locus, as well as shifts in histone modification marks (H3K4me3 and H3K27me3) at T<sub>H</sub>1-associated genes, including <em>TBX21</em> and <em>IFNG</em>. These chromatin-associated features were accompanied by increased nitric oxide production and enhanced cytotoxicity in functional assays. Collectively, these findings suggest that variation in CTCF levels is linked to coordinated epigenetic and immune-associated changes in NSCLC, supporting its potential relevance as an immuno-epigenetic factor in shaping anti-tumor immune responses.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110662"},"PeriodicalIF":3.8,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-25DOI: 10.1016/j.clim.2025.110661
Wei Qiu , Ya Huang , Yan Gu , Yichi Sun , Ping Yue , KaiDe Xia , Shichao Zhang
Emerging data have revealed that m1A modification and its regulators are key participants in tumorigenesis and progression. The cell-free miRNAs have been demonstrated to circulate stably in the serum, making them biomarker candidates for cancer diagnosis. Here we included 16,902 serum samples to develop a diagnostic signature named m1A-miRNA signature based on serum circulating m1A-related miRNAs for cancer detection. The m1A-miRNA signature presented excellent accuracy, and the area under the curve (AUC) was 0.991 in the training cohort. The diagnostic capability of the m1A-miRNA signature was not affected by sexual distinction, age and non-cancer disease. As far as distinguishing cancer types is concerned, the signature exerted superior ability in identifying the types of glioblastoma multiforme, gastric cancer and lung cancer. We also found that the m1A-miRNA signature showed a satisfactory AUC in the early diagnosis of pan-cancer. Additionally, the accuracy of the m1A-miRNA signature was further verified by clinical samples.
{"title":"A novel diagnostic signature constructed based on serum-circulating m1A-related miRNAs for cancer detection","authors":"Wei Qiu , Ya Huang , Yan Gu , Yichi Sun , Ping Yue , KaiDe Xia , Shichao Zhang","doi":"10.1016/j.clim.2025.110661","DOIUrl":"10.1016/j.clim.2025.110661","url":null,"abstract":"<div><div>Emerging data have revealed that m<sup>1</sup>A modification and its regulators are key participants in tumorigenesis and progression. The cell-free miRNAs have been demonstrated to circulate stably in the serum, making them biomarker candidates for cancer diagnosis. Here we included 16,902 serum samples to develop a diagnostic signature named m1A-miRNA signature based on serum circulating m<sup>1</sup>A-related miRNAs for cancer detection. The m1A-miRNA signature presented excellent accuracy, and the area under the curve (AUC) was 0.991 in the training cohort. The diagnostic capability of the m1A-miRNA signature was not affected by sexual distinction, age and non-cancer disease. As far as distinguishing cancer types is concerned, the signature exerted superior ability in identifying the types of glioblastoma multiforme, gastric cancer and lung cancer. We also found that the m1A-miRNA signature showed a satisfactory AUC in the early diagnosis of pan-cancer. Additionally, the accuracy of the m1A-miRNA signature was further verified by clinical samples.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110661"},"PeriodicalIF":3.8,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145846397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-24DOI: 10.1016/j.clim.2025.110660
Jun Han , Qifeng Yao , Qiuyue Huang , Zuoyou Ding , Guohao Wu
Cancer cachexia involves severe skeletal muscle and adipose tissue loss. The role of Apolipoprotein E (ApoE) in adipose remodeling remains unclear. This study investigated ApoE's function in cancer cachexia. We found cachectic patients had decreased plasma ApoE but elevated expression in subcutaneous adipose. In vitro, ApoE knockdown in adipocytes downregulated both lipogenesis and lipolysis genes. In vivo, ApoE−/− mice were protected against adipose wasting in a cachexia model. Single-cell RNA sequencing revealed ApoE deficiency altered immune cell dynamics, increasing total macrophages and enriching a specific Cbr2+ macrophage subpopulation with an M2-like phenotype. This was confirmed by immunofluorescence showing enhanced M2 macrophage infiltration in adipose tissue. We conclude that ApoE is a critical regulator of adipose homeostasis and immune modulation in cancer cachexia, representing a promising diagnostic and therapeutic target.
{"title":"Single-cell sequencing reveals APOE deletion alleviates adipose wasting in cancer cachexia via macrophage repolarization","authors":"Jun Han , Qifeng Yao , Qiuyue Huang , Zuoyou Ding , Guohao Wu","doi":"10.1016/j.clim.2025.110660","DOIUrl":"10.1016/j.clim.2025.110660","url":null,"abstract":"<div><div>Cancer cachexia involves severe skeletal muscle and adipose tissue loss. The role of Apolipoprotein E (ApoE) in adipose remodeling remains unclear. This study investigated ApoE's function in cancer cachexia. We found cachectic patients had decreased plasma ApoE but elevated expression in subcutaneous adipose. In vitro, ApoE knockdown in adipocytes downregulated both lipogenesis and lipolysis genes. In vivo, ApoE<sup>−/−</sup> mice were protected against adipose wasting in a cachexia model. Single-cell RNA sequencing revealed ApoE deficiency altered immune cell dynamics, increasing total macrophages and enriching a specific Cbr2+ macrophage subpopulation with an M2-like phenotype. This was confirmed by immunofluorescence showing enhanced M2 macrophage infiltration in adipose tissue. We conclude that ApoE is a critical regulator of adipose homeostasis and immune modulation in cancer cachexia, representing a promising diagnostic and therapeutic target.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110660"},"PeriodicalIF":3.8,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145836500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-21DOI: 10.1016/j.clim.2025.110659
Temesgen E. Andargie , Han Su , Moon Kyoo Jang , Xin Tian , Andrew H. Karaba , Sean Agbor-Enoh
The association between circulating cytokines and allograft injury due to allograft rejection (AR) remains poorly defined. We hypothesize that cytokines correlate with the degree of allograft injury during AR. This case-control study measured cytokines and cell-free DNA in 88 heart transplant plasma samples (54 AR, 34 non-rejecting (NR) controls) and 26 healthy controls. AR patients exhibited higher levels of total and percent donor-derived cfDNA (%dd-cfDNA) and proinflammatory cytokines, and lower levels of type II cytokines/chemokines and Th17/23 axis cytokines compared to NR or HCs. The cfDNA levels positively correlated with proinflammatory cytokines and negatively with MDC and cytokines of the Th17/IL-23 axis. A Lasso regression model combining cytokines and %dd-cfDNA (AUC = 0.93) showed better AR diagnostic performance than either cytokines or %dd-cfDNA alone. The study concluded that inflammatory and regulatory cytokine levels correlate with allograft injury, and combining cytokines with %dd-cfDNA may enhance AR detection.
{"title":"Systemic cytokine profiling enhances the performance of dd-cfDNA to detect cardiac rejection","authors":"Temesgen E. Andargie , Han Su , Moon Kyoo Jang , Xin Tian , Andrew H. Karaba , Sean Agbor-Enoh","doi":"10.1016/j.clim.2025.110659","DOIUrl":"10.1016/j.clim.2025.110659","url":null,"abstract":"<div><div>The association between circulating cytokines and allograft injury due to allograft rejection (AR) remains poorly defined. We hypothesize that cytokines correlate with the degree of allograft injury during AR. This case-control study measured cytokines and cell-free DNA in 88 heart transplant plasma samples (54 AR, 34 non-rejecting (NR) controls) and 26 healthy controls. AR patients exhibited higher levels of total and percent donor-derived cfDNA (%dd-cfDNA) and proinflammatory cytokines, and lower levels of type II cytokines/chemokines and Th17/23 axis cytokines compared to NR or HCs. The cfDNA levels positively correlated with proinflammatory cytokines and negatively with MDC and cytokines of the Th17/IL-23 axis. A Lasso regression model combining cytokines and %dd-cfDNA (AUC = 0.93) showed better AR diagnostic performance than either cytokines or %dd-cfDNA alone. The study concluded that inflammatory and regulatory cytokine levels correlate with allograft injury, and combining cytokines with %dd-cfDNA may enhance AR detection.</div></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":"283 ","pages":"Article 110659"},"PeriodicalIF":3.8,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145817674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/j.clim.2025.110658
Shanmuganathan Chandrakasan , Adrianna Westbrook , Linda M. Griffith , David Hagin , Sumathi Iyengar , Christina Mangurian , Chris Scalchunes , Kathleen E. Sullivan , Akiva Zablocki , Nitya Bakshi , Cynthia Sinha , Lauri M. Burroughs , Alice Y. Chan , Christopher C. Dvorak , Elie Haddad , Jennifer Heimall , Donald B. Kohn , Jennifer W. Leiding , Luigi D. Notarangelo , Sung-Yun Pai , Suhag Parikh
Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder with microthrombocytopenia, eczema, immunodeficiency, autoimmunity and malignancies resulting from WAS pathogenic variants. Prevalence of disease in heterozygous female carriers has not been described previously.
An online Qualtrics survey was designed in collaboration with the Wiskott-Aldrich Foundation, the Immune Deficiency Foundation, the Primary Immune Deficiency Treatment Consortium and Emory University to describe the incidence of thrombocytopenia, eczema, infections, autoimmune disorders, malignancies, and psychosocial factors.
193 carriers with a median age of 39 years participated in this survey. Respondents were predominantly White and were mothers of WAS patients. We observed a high prevalence of thrombocytopenia (13 %), eczema (22 %), infections (33 %) and autoimmunity (24 %) in this self-reported survey. No hematological malignancies were reported. Guilt (91 %), anxiety (41 %) and depression (44 %) were very prevalent.
Comprehensive clinical and immunologic studies of WAS carriers should be prioritized to define appropriate health screening, preventive approaches, and counselling for carriers.
Summary
This self-reported survey describes the disease burden in 193 carriers of X-linked Wiskott-Aldrich syndrome. It highlights the increased incidence of thrombocytopenia, eczema, infections and autoimmunity in WAS carriers and the need for more comprehensive studies of WAS carriers.
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