Immunology最新文献_第2页

5-FU Resistance Facilitates Immune Evasion in Esophageal Squamous Cell Carcinoma Through ADAM10-Mediated PD-L1 Shedding and Tumour Microenvironment Remodelling. 5-FU耐药性通过adam10介导的PD-L1脱落和肿瘤微环境重塑促进食管鳞状细胞癌的免疫逃避。

IF 5 3区医学

Immunology Pub Date : 2025-09-16 DOI: 10.1111/imm.70038

Bangwu Cai, Xiaowen Feng, Shujuan Luo, Aididar Nurbahati, Hong Cui, Tianyuan Peng, Wei Wang, Huifang Li, Qing Liu, Xiaomei Lu, Shutao Zheng

{"title":"5-FU Resistance Facilitates Immune Evasion in Esophageal Squamous Cell Carcinoma Through ADAM10-Mediated PD-L1 Shedding and Tumour Microenvironment Remodelling.","authors":"Bangwu Cai, Xiaowen Feng, Shujuan Luo, Aididar Nurbahati, Hong Cui, Tianyuan Peng, Wei Wang, Huifang Li, Qing Liu, Xiaomei Lu, Shutao Zheng","doi":"10.1111/imm.70038","DOIUrl":"https://doi.org/10.1111/imm.70038","url":null,"abstract":"Chemoresistance remains a major challenge in esophageal squamous cell carcinoma (ESCC) therapy, particularly resistance to 5-Fluorouracil (5-FU). This study uncovers how 5-FU resistance reprograms the tumour microenvironment, primarily through the up-regulation of ADAM10 and the release of soluble PD-L1, which collectively facilitate immune evasion. Using a 5-FU-resistant AKR mouse ESCC cell line (5-FU-AKR) and its parental counterpart, we applied third-generation DNA sequencing, proteomic analysis, and single-cell RNA sequencing to unravel the resistance-associated molecular and cellular shifts. We found that ADAM10 is significantly up-regulated in 5-FU-AKR cells, promoting soluble PD-L1 release, thereby limiting CD8+ T cell infiltration. Xenograft models further demonstrated enhanced tumourigenicity and immune exclusion in 5-FU-resistant tumours. These findings highlight a novel mechanism of immune suppression driven by ADAM10, suggesting that targeting the ADAM10-PD-L1 axis may restore anti-tumour immunity and improve treatment outcomes for 5-FU-resistant ESCC.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075282","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}

引用次数: 0

The Immune System and Cellular Senescence: A Complex Interplay in Aging and Disease. 免疫系统和细胞衰老：衰老和疾病的复杂相互作用。

IF 5 3区医学

Immunology Pub Date : 2025-09-12 DOI: 10.1111/imm.70036

Marc Ayoub, Chris Abou Jaoude, Mohamad Ayoub, Aline Hamade, Mohamad Rima

{"title":"The Immune System and Cellular Senescence: A Complex Interplay in Aging and Disease.","authors":"Marc Ayoub, Chris Abou Jaoude, Mohamad Ayoub, Aline Hamade, Mohamad Rima","doi":"10.1111/imm.70036","DOIUrl":"https://doi.org/10.1111/imm.70036","url":null,"abstract":"Immunosenescence is the process of immune dysfunction and gradual deterioration of the immune system associated with aging, while cellular senescence is the stable cell cycle arrest that can occur in non-immune or immune cells in response to stress or damage. Immunosenescence significantly impacts both the innate and adaptive immune responses and is characterised by physical changes in lymphoid organs, as well as dysfunctions in cellular and molecular mechanisms. Key features of immunosenescence include T-cell dysfunction, thymic involution, B cell aging, an imbalance in the ratio of naïve to memory cells, chronic inflammation known as inflammaging and metabolic dysregulation. This decline in immune cell diversity and functionality contributes to various age-related diseases. Therefore, restoring a more 'juvenile' immune function in aging populations, through interventions targeting immunosenescence, holds promise for alleviating many age-related diseases and promoting healthier aging. In this review, we provide a comprehensive understanding of the interplay between the immune system and senescent cells in both healthy and disease contexts. We then dissect the immune dysfunction that occurs with aging, known as immunosenescence, and explore its impact on the health of elderly individuals. Finally, we discuss recent advances in targeting immune system aging to promote healthier longevity, with a special focus on Programmed Death-Ligand 1 (PD-L1), an emerging and promising target for therapeutic intervention.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039742","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}

引用次数: 0

Enolase-1 Is a Key Regulator of Neutrophil Recruitment During Acute Inflammation. 烯醇化酶-1是急性炎症中中性粒细胞募集的关键调节因子。

IF 5 3区医学

Immunology Pub Date : 2025-09-09 DOI: 10.1111/imm.70034

Hsueh-Yen Lu, Ping-Hsiang Huang, Ting-Wei Lee, Hui-Wen Chang, Nai-Yu Chen, Yu-Jing Zhuang, Ta-Tung Yuan, Chun-Jen Chen

{"title":"Enolase-1 Is a Key Regulator of Neutrophil Recruitment During Acute Inflammation.","authors":"Hsueh-Yen Lu, Ping-Hsiang Huang, Ting-Wei Lee, Hui-Wen Chang, Nai-Yu Chen, Yu-Jing Zhuang, Ta-Tung Yuan, Chun-Jen Chen","doi":"10.1111/imm.70034","DOIUrl":"https://doi.org/10.1111/imm.70034","url":null,"abstract":"Enolase-1 (ENO1) is a moonlighting protein with multiple functions. When expressed on the cell surface, ENO1 binds plasminogen (PLG) and promotes cell migration by facilitating plasmin (PLM)-mediated extracellular matrix degradation. Here, we observed that inflammatory stimulation significantly upregulated ENO1 expression on the neutrophil surface, both in vitro and in vivo. An anti-ENO1 monoclonal antibody (mAb), 7E5, which blocks the ENO1-PLG interaction, effectively suppressed neutrophil invasion in vitro. In mouse models of acute inflammation, including lipopolysaccharide (LPS)-induced lung injury and necrotic cell challenge, 7E5 treatment markedly reduced neutrophil recruitment and neutrophil extracellular trap (NET) formation. Similarly, the PLG inhibitor tranexamic acid (TXA) attenuated neutrophil recruitment, confirming the critical role of the PLG/PLM system in neutrophil migration. These findings highlight ENO1 as a key regulator of inflammation and neutrophil infiltration. Targeting ENO1 with antibodies could be a promising strategy to mitigate tissue damage caused by excessive neutrophilic inflammation.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023163","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}

引用次数: 0

COX-2 Mediates Immune Evasion and Decreases Chemosensitivity in Breast Cancer Through Activation of the JAK2/STAT3 Signalling Pathway. COX-2通过激活JAK2/STAT3信号通路介导乳腺癌的免疫逃避和降低化疗敏感性

IF 5 3区医学

Immunology Pub Date : 2025-09-06 DOI: 10.1111/imm.70031

Guohua Liu, Peng Liu, Kai Liang, Zeshuai Zhang, Pengliang Hao, Xiumei Deng, Junlan Guo

{"title":"COX-2 Mediates Immune Evasion and Decreases Chemosensitivity in Breast Cancer Through Activation of the JAK2/STAT3 Signalling Pathway.","authors":"Guohua Liu, Peng Liu, Kai Liang, Zeshuai Zhang, Pengliang Hao, Xiumei Deng, Junlan Guo","doi":"10.1111/imm.70031","DOIUrl":"https://doi.org/10.1111/imm.70031","url":null,"abstract":"With 1 in every 20 women afflicted, breast cancer is the most frequent malignant tumour in women and a significant health burden on women. Drug resistance in cancer is the key problem limiting current therapy approaches. Cyclooxygenase-2 (COX-2, namely PTGS2) is linked to immune evasion and chemoresistance in tumour cells, and it is frequently overexpressed in many forms of cancer. It is currently unclear how precisely this regulatory link functions in breast cancer, though. COX-2 expression in breast cancer was verified by this investigation. COX-2 knockdown was used to confirm COX-2 function in the malignant development of tumour cells and the stimulation of the JAK2/STAT3 signalling pathway. The survival of tumour cells was then assessed by co-culturing with CD8+ T cells or receiving chemotherapy after COX-2 was knocked down. To examine the function of the JAK2/STAT3 signalling system, cells from each group were then treated with a combination of COX-2 overexpression plasmid and JAK2/STAT3 inhibitor. The tissues and cells of breast cancer had elevated expression levels of COX-2. Following the downregulation of COX-2, breast cancer cells showed enhanced apoptosis, lower susceptibility to chemotherapy, impeded proliferation and epithelial-mesenchymal transition and were more readily destroyed by CD8+ T lymphocytes. Nevertheless, the opposite effects were shown when COX-2 was overexpressed, and JAK2/STAT3 inhibitors were able to reverse these effects. COX-2 activated the JAK2/STAT3 signalling pathway, which in turn promoted immune evasion and decreased chemosensitivity in breast cancer.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006024","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}

引用次数: 0

Dendritic Cell-Derived Extracellular Vesicles as Therapeutic Cancer Vaccines: Mechanisms and Optimization Strategies. 树突状细胞衍生的细胞外囊泡作为治疗性癌症疫苗：机制和优化策略。

IF 5 3区医学

Immunology Pub Date : 2025-09-02 DOI: 10.1111/imm.70033

Jonathan Shpigelman, Krishna Rao

引用次数: 0

Microneedle-Delivered Multivalent MPXV DNA Vaccines Induce Promising Immunity Profiles and Cross-Protection in Mice. 微针递送的多价MPXV DNA疫苗在小鼠中诱导有希望的免疫谱和交叉保护

IF 5 3区医学

Immunology Pub Date : 2025-09-02 DOI: 10.1111/imm.70030

Yawei Wang, Xueting Cheng, Baoying Huang, Ruixiao Tan, Feng Fan, Li Zhao, Wenling Wang, Fei Ye, Yao Deng, Xiaoming Gao, Bin Wang, Wenjie Tan

{"title":"Microneedle-Delivered Multivalent MPXV DNA Vaccines Induce Promising Immunity Profiles and Cross-Protection in Mice.","authors":"Yawei Wang, Xueting Cheng, Baoying Huang, Ruixiao Tan, Feng Fan, Li Zhao, Wenling Wang, Fei Ye, Yao Deng, Xiaoming Gao, Bin Wang, Wenjie Tan","doi":"10.1111/imm.70030","DOIUrl":"https://doi.org/10.1111/imm.70030","url":null,"abstract":"Traditional DNA vaccines, typically administered via intramuscular injection with electroporation (IM-E), often cause discomfort and require trained personnel. Addressing these challenges, we developed multivalent DNA vaccines targeting both intracellular mature virion (IMV) and extracellular enveloped virion (EEV) proteins of the monkeypox virus (MPXV), designated as M2 (A29L, B6R), M3 (A29L, B6R, M1R) and M4 (A29L, B6R, M1R, A35R). These vaccine constructs were formulated into dissolvable microneedle array patches (D-MAPs) for intradermal delivery. Comparative studies in mice demonstrated that D-MAPs achieved approximately 70% delivery efficiency and elicited robust humoral immune responses in mice, including antigen-specific IgG and cross-neutralising antibodies against MPXV, VACV and ECTV-comparable to those induced by IM-E. Furthermore, D-MAP immunisation induced stronger T cell responses, particularly in the draining lymph nodes. Importantly, the multivalent DNA vaccines-especially M3 and M4-conferred substantial protection against lethal VACV-WR challenge, achieving levels of protection comparable to the traditional replication-competent smallpox vaccine TianTan (VTT), with significant viral suppression and mitigation of pathological damage. Collectively, this study provided valuable insights for the development of innovative MPXV DNA vaccines, highlighting a minimally invasive and suitable for field application with D-MAP with broad potential for combating mpox outbreaks and future orthopoxvirus pandemics.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952584","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}

引用次数: 0

Human Gut Commensal Bacteroides fragilis Suppresses Mucin Production and Alters Microbiota Composition Resulting in Accelerated Type 1 Diabetes in Mice. 人类肠道共生脆弱拟杆菌抑制粘蛋白产生并改变微生物群组成，导致小鼠1型糖尿病加速

IF 5 3区医学

Immunology Pub Date : 2025-08-26 DOI: 10.1111/imm.70032

Radhika R Gudi, Harrison Taylor, Benjamin M Johnson, Ruchika Maurya, Mary E Mulligan, Loni Carter, Caroline Westwater, Chenthamarakshan Vasu

{"title":"Human Gut Commensal Bacteroides fragilis Suppresses Mucin Production and Alters Microbiota Composition Resulting in Accelerated Type 1 Diabetes in Mice.","authors":"Radhika R Gudi, Harrison Taylor, Benjamin M Johnson, Ruchika Maurya, Mary E Mulligan, Loni Carter, Caroline Westwater, Chenthamarakshan Vasu","doi":"10.1111/imm.70032","DOIUrl":"https://doi.org/10.1111/imm.70032","url":null,"abstract":"Type 1 diabetes (T1D) in humans is associated with a higher Bacteroidetes:Firmicutes ratio and a higher abundance of Bacteroides genus members. Bacteroides fragilis (BF) is an integral component of the human colonic commensal microbiota. Here, we show that gut colonisation of specific pathogen-free (SPF) non-obese diabetic (NOD) mice by BF at a juvenile age induces a pro-inflammatory immune response and accelerated disease progression. NOD mice born to BF-monocolonised parents not only showed rapid disease progression compared to germ-free (GF) controls but also preserved accelerated disease onset and higher disease incidence upon conventionalisation, suggesting that BF contributes to a pro-inflammatory response and autoimmunity in T1D. Interestingly, we found that while gut microbiota composition was different in control and BF-colonised SPF mice, the presence of BF alone could significantly impact the acquisition of microbial communities upon conventionalisation of gnotobiotic mice. Bulk RNAseq analysis of colon tissues revealed profound differences in the gene expression pattern of GF and BF-monocolonised mice as well as their conventionalised counterparts, shedding light on the probable mechanisms contributing to accelerated disease onset in mice that are exposed to BF. We found that mucin production is downregulated and the abundance of mucin degraders such as Akkermansia muciniphila is profoundly lower in BF-colonised mice. Overall, these studies demonstrate that early life acquisition of BF-like distal gut commensals could have profound modulatory effects on the eventual overall gut physiology, microbiota structure, immune function, and β-cell specific autoimmune outcomes under genetic susceptibility.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952642","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}

引用次数: 0

Tertiary Lymphoid Structures Predict Prognosis and Immune Checkpoint Inhibitor Efficacy in Lung Squamous Cell Carcinoma. 三级淋巴结构预测肺鳞癌的预后和免疫检查点抑制剂的疗效。

IF 5 3区医学

Immunology Pub Date : 2025-08-15 DOI: 10.1111/imm.70027

Kuifei Chen, Suna Zhou, Pin Zhou, Zhenwei Sun, Yixiu Xu, Ziran Chen, Liangmin Zhang, Wenhu Pi, Meifu Gan, Haihua Yang

{"title":"Tertiary Lymphoid Structures Predict Prognosis and Immune Checkpoint Inhibitor Efficacy in Lung Squamous Cell Carcinoma.","authors":"Kuifei Chen, Suna Zhou, Pin Zhou, Zhenwei Sun, Yixiu Xu, Ziran Chen, Liangmin Zhang, Wenhu Pi, Meifu Gan, Haihua Yang","doi":"10.1111/imm.70027","DOIUrl":"https://doi.org/10.1111/imm.70027","url":null,"abstract":"Lung squamous cell carcinoma (LUSC) is a highly mortal cancer. Tertiary lymphoid structures (TLSs) play a crucial role in creating a specific and essential environment for the development of cellular and humoral immune responses against tumours. This study investigated the effect of TLSs on prognosis and the prediction of immunotherapy efficacy in LUSC. To investigate the association between TLSs and clinicopathological features, haematoxylin and eosin staining and multiple immunofluorescence staining were performed. A comparative examination of survival and the factors influencing it was carried out between the TLS-/+, high and low TLS density, immature tertiary lymphoid structures (imTLS) and mature tertiary lymphoid structures (mTLS) groups of patients. To further analyse the prognostic value of TLSs in the immunotherapy cohort of patients with LUSC, two hundred and ninety-seven patients with LUSC were enrolled in this study. Of these, 129 patients were harbouring TLS+. Cramer's V relationships analysis revealed that both Stage (p = 0.029) and PD-L1 ≥ 50% (p = 0.011) were significant predictors of TLS+. Cox proportional hazards model multivariate analysis showed that the TLS+ (p = 0.037), high TLS density (p = 0.014) and mTLS (p = 0.001) were associated with better overall survival (OS) in LUSC patients. Multivariate analyses confirmed that TLS+ was an independent prognostic predictor for OS in the LUSC immunotherapy cohort (p = 0.021). This study provided evidence that LUSC patients with TLS+, high TLS density and mTLS had a favourable prognosis, suggesting that TLSs are an independent positive prognostic factor for LUSC patients.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859081","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}

引用次数: 0

Co-Existence of IL6ST and MEFV Pathogenic Variant in a Patient With Hyper-IgE Syndrome. 高ige综合征患者IL6ST和MEFV致病变异共存

IF 5 3区医学

Immunology Pub Date : 2025-08-12 DOI: 10.1111/imm.70029

Hulya Kose, Muruvvet Yanaz, Akcahan Akalin

引用次数: 0

Exercise Duration Modulates Cortisol Release and Chronic Cortisol Exposure Jeopardises T Cell Effector Functions. 运动时间调节皮质醇释放，慢性皮质醇暴露损害T细胞效应功能。

IF 5 3区医学

Immunology Pub Date : 2025-08-12 DOI: 10.1111/imm.70028

Thy Viet Luu, Line Fleischer Hach, Tina Seremet, Katharina Leuchte, Per Thor Straten, Gitte Holmen Olofsson

{"title":"Exercise Duration Modulates Cortisol Release and Chronic Cortisol Exposure Jeopardises T Cell Effector Functions.","authors":"Thy Viet Luu, Line Fleischer Hach, Tina Seremet, Katharina Leuchte, Per Thor Straten, Gitte Holmen Olofsson","doi":"10.1111/imm.70028","DOIUrl":"https://doi.org/10.1111/imm.70028","url":null,"abstract":"Psychological stress has been linked to increased incidence and mortality of cancer. During stress, cortisol is released into circulation and regulates cellular processes including immune activity by acting on glucocorticoid receptors (GCRs) expressed by target cells. Chronic stress-induced cortisol has been suggested to promote tumour progression and compromise the efficacy of cancer treatments. Conversely, cortisol is also transiently secreted during exercise. Although exercise has been suggested to have beneficial effects against cancer, the impact of exercise-elevated cortisol on immune cell functions remains poorly understood. Here we studied the dynamics of cortisol secretion following exercise and how cortisol affects effector functions of T cells in the context of acute versus chronic stress. We show that 40 min of acute, high-intensity exercise in healthy adults significantly increased stable circulating cortisol levels whereas a 5-min sprint failed to. Acute exposure to cortisol for 4 h showed no negative effects on the proliferation, cytokine release, or killing activity of human CD3+ T cells. In contrast, chronic cortisol dampened these T cell effector functions. Furthermore, chronic cortisol exposure induced the proliferation of several cancer cell lines. Our findings highlight the opposing effects of cortisol during acute stress, such as exercise, compared to chronic stress, on cancer cells and T cells. This suggests an important potential in targeting cortisol signalling to enhance cancer immunotherapy.","PeriodicalId":13508,"journal":{"name":"Immunology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835006","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}

引用次数: 0