Pub Date : 2026-02-04DOI: 10.1016/j.clim.2026.110679
Awatef Ben Jemaa, Mouna Ben Azaiez, Sataa Sallami, Yassine Nouira, Ezzeddine Ghazouani, Ridha Oueslati
This study explored the relationship between systemic cytokines and PSA-PSMA phenotypes in benign prostatic hyperplasia (BPH) and prostate cancer (PCa), including hormonal therapy response. Serum cytokines (IL-6, TNF-α, IL-10, IL-17 A, TGF-β1) and PSA were quantified, while tissue PSA, PSMA, CD34, TRAF-6, and phosphorylated STAT3 (Ser727, Tyr705) were evaluated immunohistochemically. AR and AR-V7 mRNA expression were assessed by RT-PCR. PCa patients exhibited elevated IL-6 and TGF-β1, higher PSMA and CD34, and reduced tissue PSA compared to BPH. pSTAT3 (Tyr705) increased, whereas pSTAT3 (Ser727) decreased in PCa. In hormone-refractory PCa, TGF-β1 and PSMA were elevated, while PSA declined. AR-V7 was largely absent, and TRAF-6 showed no hormonal difference. These findings suggest IL-6/STAT3 and TGF-β1/TRAF-6 pathways modulate PSA-PSMA dynamics, with TGF-β1/TRAF-6 particularly linked to hormone-refractory progression. Cytokine-mediated signaling may inform PCa diagnosis, prognosis, and therapeutic targeting.
{"title":"TGF-β1/TRAF-6 and IL-6/STAT-3 pathways in PSA-PSMA phenotypes of hormone-sensitive and hormone-refractory prostate Cancer.","authors":"Awatef Ben Jemaa, Mouna Ben Azaiez, Sataa Sallami, Yassine Nouira, Ezzeddine Ghazouani, Ridha Oueslati","doi":"10.1016/j.clim.2026.110679","DOIUrl":"https://doi.org/10.1016/j.clim.2026.110679","url":null,"abstract":"<p><p>This study explored the relationship between systemic cytokines and PSA-PSMA phenotypes in benign prostatic hyperplasia (BPH) and prostate cancer (PCa), including hormonal therapy response. Serum cytokines (IL-6, TNF-α, IL-10, IL-17 A, TGF-β1) and PSA were quantified, while tissue PSA, PSMA, CD34, TRAF-6, and phosphorylated STAT3 (Ser727, Tyr705) were evaluated immunohistochemically. AR and AR-V7 mRNA expression were assessed by RT-PCR. PCa patients exhibited elevated IL-6 and TGF-β1, higher PSMA and CD34, and reduced tissue PSA compared to BPH. pSTAT3 (Tyr705) increased, whereas pSTAT3 (Ser727) decreased in PCa. In hormone-refractory PCa, TGF-β1 and PSMA were elevated, while PSA declined. AR-V7 was largely absent, and TRAF-6 showed no hormonal difference. These findings suggest IL-6/STAT3 and TGF-β1/TRAF-6 pathways modulate PSA-PSMA dynamics, with TGF-β1/TRAF-6 particularly linked to hormone-refractory progression. Cytokine-mediated signaling may inform PCa diagnosis, prognosis, and therapeutic targeting.</p>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":" ","pages":"110679"},"PeriodicalIF":3.8,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131298","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}
Background: Tumor-associated autoantibodies (TAAbs) represent promising biomarkers for tumor diagnosis. This study aimed to evaluate the prognostic value of anti- Dihydrolipoamide S-acetyltransferase (DLAT) AAb in breast cancer (BC).
Methods: Levels of plasma anti-DLAT AAb were measured by ELISA in a total of 1013 samples from BC patients, patients with benign breast nodules (BN), and healthy controls (NC). Western blot was performed to confirm the ELISA results. The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases were used to analyze the expression levels of DLAT in tumor and normal breast tissues from BC patients.
Results: Plasma anti-DLAT AAb levels were decreased in BC compared to NC and BN, achieving AUCs of 0.803 (P < 0.0001) and 0.591 (P < 0.0001), respectively. Among individuals under 45 years old, anti-DLAT AAb showed high power in distinguishing BC and BC at early-stage from NC, yielding an AUC of 0.873 (P < 0.0001) and 0.845 (P < 0.0001). Besides, anti-DLAT AAb distinguished BC from BN with an AUC of 0.617 (P = 0.0016) in individuals under 45 while there was no difference between them above 45. Combining anti-DLAT AAb with CEA improved the AUCs to 0.824 (P < 0.0001) and 0.623 (P < 0.0001) for distinguishing BC from NC and BN. This combination also achieved higher AUCs of 0.891 (P < 0.0001) and 0.635 (P = 0.0003) for distinguishing BC from NC and BN among individuals under 45 years old.
Conclusions: These findings suggest that anti-DLAT AAb shows potential for BC diagnosis, especially among individuals under 45 years old. Besides, multicenter validation should be carried out to confirm this finding in the future.
{"title":"Plasma anti-DLAT autoantibody as a novel diagnostic biomarker in breast cancer.","authors":"Qianwei Zhao, Ludan Zhang, Peiqi Yu, Jingjing Liu, Tingjiang He, Yunhui Qu, Anqi Cheng, Fang Xu, Liping Dai","doi":"10.1016/j.clim.2026.110678","DOIUrl":"10.1016/j.clim.2026.110678","url":null,"abstract":"<p><strong>Background: </strong>Tumor-associated autoantibodies (TAAbs) represent promising biomarkers for tumor diagnosis. This study aimed to evaluate the prognostic value of anti- Dihydrolipoamide S-acetyltransferase (DLAT) AAb in breast cancer (BC).</p><p><strong>Methods: </strong>Levels of plasma anti-DLAT AAb were measured by ELISA in a total of 1013 samples from BC patients, patients with benign breast nodules (BN), and healthy controls (NC). Western blot was performed to confirm the ELISA results. The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases were used to analyze the expression levels of DLAT in tumor and normal breast tissues from BC patients.</p><p><strong>Results: </strong>Plasma anti-DLAT AAb levels were decreased in BC compared to NC and BN, achieving AUCs of 0.803 (P < 0.0001) and 0.591 (P < 0.0001), respectively. Among individuals under 45 years old, anti-DLAT AAb showed high power in distinguishing BC and BC at early-stage from NC, yielding an AUC of 0.873 (P < 0.0001) and 0.845 (P < 0.0001). Besides, anti-DLAT AAb distinguished BC from BN with an AUC of 0.617 (P = 0.0016) in individuals under 45 while there was no difference between them above 45. Combining anti-DLAT AAb with CEA improved the AUCs to 0.824 (P < 0.0001) and 0.623 (P < 0.0001) for distinguishing BC from NC and BN. This combination also achieved higher AUCs of 0.891 (P < 0.0001) and 0.635 (P = 0.0003) for distinguishing BC from NC and BN among individuals under 45 years old.</p><p><strong>Conclusions: </strong>These findings suggest that anti-DLAT AAb shows potential for BC diagnosis, especially among individuals under 45 years old. Besides, multicenter validation should be carried out to confirm this finding in the future.</p>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":" ","pages":"110678"},"PeriodicalIF":3.8,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123692","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 : 2026-02-02DOI: 10.1016/j.clim.2026.110676
Susanna Scaglioni, Andrea Lombardi, Giacomo M Butta, Giorgio Bozzi, Matteo Centazzo, Bianca Mariani, Antonio Muscatello, Patrizia Bono, Lorena Donnici, Matteo Conti, Riccardo Nodari, Annapaola Callegaro, Edoardo Scarpa, Renata Grifantini, Sergio Abrignani, Raffaele De Francesco, Andrea Gori, Alessandra Bandera, Lara Manganaro
Vaccination triggers both humoral and cellular immune responses, generating memory T cells that ensure long-term protection. Among these, stem cell-like memory T cells (TSCM) are crucial for durable immunity due to their self-renewal and multipotency. In people with HIV (PWHIV), vaccine-induced responses can be weakened by persistent immune dysfunction. In this study, we longitudinally analyzed T cell memory responses following mRNA-1273 vaccination in PWHIV. Individuals with incomplete immune reconstitution (CD4+ < 500 cells/μL, CD4/CD8 < 0.4) showed reduced frequencies of Spike-specific CD4+ TSCM, lower levels of TCF-1 and higher expression of immune checkpoint molecules. We identified a subset of PD-1+TIGIT+ CD4+ TSCM and TCM cells that phenotypically resemble CD8+ exhausted-like progenitors (TPEX) and are enriched in PWHIV with poor immune recovery. Modulation of the Wnt/mTORs pathway via GSK3β inhibition restored TCF-1 expression and partially rescued antigen responsiveness, highlighting a potential strategy to improve vaccine efficacy in PWHIV.
{"title":"HIV patients with poor immune recovery show exhausted CD4<sup>+</sup> stem cell memory cells and impaired COVID-19 vaccine response.","authors":"Susanna Scaglioni, Andrea Lombardi, Giacomo M Butta, Giorgio Bozzi, Matteo Centazzo, Bianca Mariani, Antonio Muscatello, Patrizia Bono, Lorena Donnici, Matteo Conti, Riccardo Nodari, Annapaola Callegaro, Edoardo Scarpa, Renata Grifantini, Sergio Abrignani, Raffaele De Francesco, Andrea Gori, Alessandra Bandera, Lara Manganaro","doi":"10.1016/j.clim.2026.110676","DOIUrl":"10.1016/j.clim.2026.110676","url":null,"abstract":"<p><p>Vaccination triggers both humoral and cellular immune responses, generating memory T cells that ensure long-term protection. Among these, stem cell-like memory T cells (T<sub>SCM</sub>) are crucial for durable immunity due to their self-renewal and multipotency. In people with HIV (PWHIV), vaccine-induced responses can be weakened by persistent immune dysfunction. In this study, we longitudinally analyzed T cell memory responses following mRNA-1273 vaccination in PWHIV. Individuals with incomplete immune reconstitution (CD4<sup>+</sup> < 500 cells/μL, CD4/CD8 < 0.4) showed reduced frequencies of Spike-specific CD4<sup>+</sup> T<sub>SCM</sub>, lower levels of TCF-1 and higher expression of immune checkpoint molecules. We identified a subset of PD-1<sup>+</sup>TIGIT<sup>+</sup> CD4<sup>+</sup> T<sub>SCM</sub> and T<sub>CM</sub> cells that phenotypically resemble CD8<sup>+</sup> exhausted-like progenitors (T<sub>PEX</sub>) and are enriched in PWHIV with poor immune recovery. Modulation of the Wnt/mTORs pathway via GSK3β inhibition restored TCF-1 expression and partially rescued antigen responsiveness, highlighting a potential strategy to improve vaccine efficacy in PWHIV.</p>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":" ","pages":"110676"},"PeriodicalIF":3.8,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118084","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}
Asprosin, a recently identified adipokine involved in metabolic and inflammatory processes. The case-control study was conducted to explore how asprosin is involved in the pathogenesis of rheumatoid arthritis (RA). 205 RA patients and 205 healthy controls were included, and MH7A cells were used for in vitro studies. Plasma asprosin was elevated in RA patients [11.4 (8.2, 15.6) ng/mL] compared to healthy controls [9.3 (7.5, 10.5) ng/mL] (Z = 5.978, P < 0.001) and exhibited moderate diagnostic accuracy (AUC = 0.67). Asprosin significantly enhanced the proliferation of synovial fibroblasts and upregulated the proinflammatory cytokines, while promoting their migratory and invasive capacities. TNF-α led to a marked downregulation of PPAR-γ, which was associated with increased asprosin levels, treatment with rosiglitazone effectively attenuated asprosin overproduction. Elevated circulating asprosin levels serve as an independent risk factor for RA and demonstrate promising diagnostic potential. PPAR-γ-mediated overexpression of asprosin contributes to synovial fibroblast dysfunction, suggesting a pathogenic role in RA development.
Asprosin，一种最近发现的脂肪因子，参与代谢和炎症过程。本病例对照研究旨在探讨asprosin如何参与类风湿关节炎（RA）的发病机制。纳入205名RA患者和205名健康对照者，并使用MH7A细胞进行体外研究。与健康对照组相比，RA患者血浆asprosin升高[11.4 (8.2,15.6)ng/mL] [9.3 (7.5, 10.5) ng/mL] (Z = 5.978，P
{"title":"Elevated asprosin expression exacerbates synovial inflammation by PPAR-γ-dependent mechanisms in rheumatoid arthritis.","authors":"Shu-Zhen Xu, Sha-Sha Tao, Peng Wang, Hai-Fen Wei, Yu-Tong Tan, Jian Tang, Zhu Chen, Hai-Feng Pan","doi":"10.1016/j.clim.2026.110677","DOIUrl":"10.1016/j.clim.2026.110677","url":null,"abstract":"<p><p>Asprosin, a recently identified adipokine involved in metabolic and inflammatory processes. The case-control study was conducted to explore how asprosin is involved in the pathogenesis of rheumatoid arthritis (RA). 205 RA patients and 205 healthy controls were included, and MH7A cells were used for in vitro studies. Plasma asprosin was elevated in RA patients [11.4 (8.2, 15.6) ng/mL] compared to healthy controls [9.3 (7.5, 10.5) ng/mL] (Z = 5.978, P < 0.001) and exhibited moderate diagnostic accuracy (AUC = 0.67). Asprosin significantly enhanced the proliferation of synovial fibroblasts and upregulated the proinflammatory cytokines, while promoting their migratory and invasive capacities. TNF-α led to a marked downregulation of PPAR-γ, which was associated with increased asprosin levels, treatment with rosiglitazone effectively attenuated asprosin overproduction. Elevated circulating asprosin levels serve as an independent risk factor for RA and demonstrate promising diagnostic potential. PPAR-γ-mediated overexpression of asprosin contributes to synovial fibroblast dysfunction, suggesting a pathogenic role in RA development.</p>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":" ","pages":"110677"},"PeriodicalIF":3.8,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118107","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 : 2026-01-21DOI: 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}
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