Frontiers in Immunology最新文献

{"title":"Editorial: The immune response to therapeutic antibodies.","authors":"Michael G Tovey, Arno J Kromminga, Daniel T Mytych","doi":"10.3389/fimmu.2025.1554297","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1554297","url":null,"abstract":"","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1554297"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11848674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD38 deficiency leads to a defective short-lived transcriptomic response to chronic graft-versus-host disease induction, involving purinergic signaling-related genes and distinct transcriptomic signatures associated with lupus.","authors":"Mercedes Zubiaur, Laura C Terrón-Camero, Fernando Gordillo-González, Eduardo Andrés-León, Alicia Barroso-Del Jesús, Luz María Canet-Antequera, María M Pérez Sánchez-Cañete, África Martínez-Blanco, Marilú Domínguez-Pantoja, María Botia-Sánchez, Sonia Pérez-Cabrera, Nerea Bello-Iglesias, Antonio Alcina, Ana-Clara Abadía-Molina, Fuencisla Matesanz, Esther Zumaquero, Ramón Merino, Jaime Sancho","doi":"10.3389/fimmu.2025.1441981","DOIUrl":"10.3389/fimmu.2025.1441981","url":null,"abstract":"<p><p>This study aimed to elucidate the transcriptomic signatures and dysregulated pathways associated with the autoimmune response in <i>Cd38^-/-</i> mice compared to wild-type (WT) mice within the bm12 chronic graft-versus-host disease (cGVHD) lupus model. We conducted bulk RNA sequencing on peritoneal exudate cells (PECs) and spleen cells (SPC) at two and four weeks following adoptive cell transfer. We also analyzed cells from healthy, untreated mice. These analyses revealed a sustained upregulation of a transcriptional profile of purinergic receptors and ectonucleotidases in cGVHD WT PECs, which displayed a coordinated expression with several type I interferon-stimulated genes (ISGs) and with key molecules involved in the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, two hallmarks in the lupus pathology. A second purinergic receptor transcriptomic profile, which included <i>P2rx7</i> and <i>P2rx4</i>, showed a coordinated gene expression of the components of the NLRP3 inflammasome with its potential activators. These processes were transcriptionally less active in cGVHD <i>Cd38^-/-</i> PECs than in WT PECs. We have also shown evidence of a distinct enrichment in pathways signatures that define processes such as Ca²⁺ ion homeostasis, cell division, phagosome, autophagy, senescence, cytokine/cytokine receptor interactions, Th17 and Th1/Th2 cell differentiation in <i>Cd38^-/-</i> versus WT samples, which reflected the milder inflammatory and autoimmune response elicited in <i>Cd38^-/-</i> mice relative to WT counterparts in response to the allogeneic challenge. Last, we have shown an intense metabolic reprogramming toward oxidative phosphorylation in PECs and SPC from cGVHD WT mice, which may reflect an increased cellular demand for oxygen consumption, in contrast to PECs and SPC from cGVHD <i>Cd38^-/-</i> mice, which showed a short-lived metabolic effect at the transcriptomic level. Overall, these findings support the pro-inflammatory and immunomodulatory role of CD38 during the development of the cGVHD-lupus disease.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1441981"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Tuberculosis and humoral immunity.","authors":"Taru S Dutt, José Alberto Choreño-Parra","doi":"10.3389/fimmu.2025.1562567","DOIUrl":"10.3389/fimmu.2025.1562567","url":null,"abstract":"","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1562567"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of intratumoral microbiota in tumor metastasis: a special perspective of microorganisms in tumorigenesis and clinical therapeutics.","authors":"Lei Zhang, Xichu Duan, Yanhua Zhao, Dejiu Zhang, Yuan Zhang","doi":"10.3389/fimmu.2025.1526589","DOIUrl":"10.3389/fimmu.2025.1526589","url":null,"abstract":"<p><p>Tumor metastasis is the main cause of therapeutic failure and mortality in cancer patients. The intricate metastastic process is influenced by both the intrinsic properties of tumor cells and extrinsic factors, such as microorganisms. Notably, some microbiota have been discovered to colonize tumor tissues, collectively known as intratumoral microbiota. Intratumoral microbiota can modulate tumor progression through multiple mechanisms, including regulating immune responses, inducing genomic instability and gene mutations, altering metabolic pathways, controlling epigenetic pathways, and disrupting cancer-related signaling pathways. Furthermore, intratumoral microbiota have been shown to directly impact tumor metastasis by regulating cell adhesion, stem cell plasticity and stemness, mechanical stresses and the epithelial-mesenchymal transition. Indirectly, they may affect tumor metastasis by modulating the host immune system and the tumor microenvironment. These recent findings have reshaped our understanding of the relationship between microorganims and the metastatic process. In this review, we comprehensively summarize the existing knowledge on tumor metastasis and elaborate on the properties, origins and carcinogenic mechanisms of intratumoral microbiota. Moreover, we explore the roles of intratumoral microbiota in tumor metastasis and discuss their clinical implications. Ongoing research in this field will establish a solid foundation for novel therapeutic strategies and clinical treatments for various tumors.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1526589"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of high-sensitivity C-reactive protein with hepatic fibrosis in patients with metabolic dysfunction-associated steatotic liver disease.","authors":"Yunfei Wu, Guojun Zheng, Fan Zhang, Wenjian Li","doi":"10.3389/fimmu.2025.1544917","DOIUrl":"10.3389/fimmu.2025.1544917","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the association between high-sensitivity C-reactive protein (hsCRP) levels and hepatic fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and assess its predictive efficacy.</p><p><strong>Methods: </strong>The study included 1,477 participants from the United States and 1,531 from China diagnosed with MASLD. Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were assessed by vibration-controlled transient elastography (VCTE) to evaluate the presence and degree of hepatic fibrosis and steatosis. The relationship between hsCRP levels and hepatic fibrosis in MASLD patients was examined using multivariable-adjusted and restricted cubic spline (RCS) models. Additionally, subgroup analyses were conducted to investigate the potential heterogeneity among different characteristic subgroups.</p><p><strong>Results: </strong>The results demonstrated a significant correlation between elevated hsCRP levels and an increased risk of significant fibrosis, advanced fibrosis, and cirrhosis in the US cohort of MASLD patients (OR 2.22, 1.69, and 2.85, respectively; all P <0.05). The results of the Chinese cohort were consistent with those of the US cohort, and there was a significant and positive correlation between hsCRP levels and the risk of hepatic fibrosis in patients with MASLD (OR 2.53, 3.85, and 3.78, respectively, all P <0.001). The RCS analysis revealed a significant non-linear relationship between hsCRP levels and the degree of hepatic fibrosis, with disparate inflection point values observed across different cohorts (approximately 9 mg/L in the US cohort and 4 mg/L in the Chinese cohort). The impact of hsCRP levels on the risk of hepatic fibrosis varied across different subgroups with distinct characteristics.</p><p><strong>Conclusion: </strong>The present study demonstrated a significant correlation between hsCRP levels and the degree of hepatic fibrosis in patients with MASLD, with notable dose-response relationships and subgroup differences.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1544917"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bibliometric insight into neoadjuvant immunotherapy in non-small cell lung cancer: trends, collaborations, and future avenues.","authors":"Pengliang Xu, Huanming Yu, Hupo Bian, Dan Jia, Wenhui Li, Hongfeng Dong, Xiuhua Peng","doi":"10.3389/fimmu.2025.1533651","DOIUrl":"10.3389/fimmu.2025.1533651","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant immunotherapy (NIT) is a rapidly emerging paradigm for advanced resectable non-small cell lung cancer (NSCLC). However, there is no bibliometric analysis in this research field.</p><p><strong>Objective: </strong>To analyze the hotspots and trends in the research of NIT for NSCLC and provide a reference for the study of NIT for lung cancer in China.</p><p><strong>Methods: </strong>Retrieve literature related to NIT for NSCLC from Web of Science, PubMed, and Scopus databases up to September 10, 2024. Use CiteSpace and VOSviewer software visualization software to analyze the keywords of country, author, institution, and literature.</p><p><strong>Results: </strong>There were 1575 references, and the overall annual publication volume showed an upward trend; Forde and Patrick M have published the most articles in the literature. The research hotspots mainly focus on chemotherapy, NIT for NSCLC, immunotherapy, neoadjuvant chemotherapy, pathological reactions, etc.</p><p><strong>Conclusions: </strong>This is the first bibliometric study comprehensively summarizing NIT's research trends and development in NSCLC. Our bibliometric assessment provides a panoramic view of the research milieu surrounding NIT for NSCLC, encapsulating the present state, evolving trends, and potential future directions, particularly emphasizing the promise of immunochemotherapy.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1533651"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrospinal fluid and serum cytokine profiles in severe viral encephalitis with implications for refractory status epilepticus: a retrospective observational study.","authors":"Peipei Huang, Fan Yang, Ruirui Dong, Lijun Wen, Qiuling Zang, Dandan Song, Junshuang Guo, Yating Wang, Ruike Zhang, Zhiping Ren, Jinjin Qin, Junfang Teng, Wang Miao","doi":"10.3389/fimmu.2025.1528763","DOIUrl":"10.3389/fimmu.2025.1528763","url":null,"abstract":"<p><strong>Background: </strong>To identify new intervention targets, we explored the correlation between cytokines and the development of refractory status epilepticus (RSE) in patients with severe viral encephalitis (SVE).</p><p><strong>Methods: </strong>We examined the characteristics of 14 cytokines in the cerebrospinal fluid (CSF) and serum, analyzing their correlation with acute symptomatic seizures and prognosis. Furthermore, we conducted a dynamic analysis of differences and correlations in the expression of cytokines among patients with SVE without seizures, those with controlled seizures, and those with RSE.</p><p><strong>Results: </strong>We included 161 patients with SVE; the incidence of seizures was 55.2%, and the mortality rate was 5.5%. Notably, 18.9% of these patients developed RSE, with a mortality rate of 20%. During the early stage of SVE, CSF interleukin (IL)-6 and IL-8 levels were significantly higher, declining over time and affecting the prognosis. CSF IL-6 and IL-8 levels were significantly elevated in the RSE group compared to patients without seizures and with controlled seizures, decreasing gradually and independently of serum cytokine levels. CSF IL-8 and age were independent risk factors for RSE, with clinical utility.</p><p><strong>Conclusions: </strong>Patients with SVE exhibit intrathecal cytokine storms, primarily characterized by elevated levels of IL-6 and IL-8, which influence prognosis. The strong and persistent hyperinflammation underscored by CSF IL-6 and IL-8 is associated with the occurrence and development of RSE; thus, CSF IL-8 and age are independent risk factors for SVE with RSE, indicating potential anti-inflammatory intervention targets.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1528763"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing transcriptomic biomarkers for TAVO412 utilizing next generation sequencing analyses of preclinical tumor models.","authors":"Ying Jin, Peng Chen, Huajun Zhou, Guangmao Mu, Simin Wu, Zhengxia Zha, Bin Ma, Chao Han, Mark L Chiu","doi":"10.3389/fimmu.2025.1505868","DOIUrl":"10.3389/fimmu.2025.1505868","url":null,"abstract":"<p><strong>Introduction: </strong>TAVO412, a multi-specific antibody targeting epidermal growth factor receptor (EGFR), mesenchymal epithelial transition factor (c-Met), and vascular endothelial growth factor A (VEGF-A), is undergoing clinical development for the treatment of solid tumors. TAVO412 has multiple mechanisms of action for tumor growth inhibition that include shutting down the EGFR, c-Met, and VEGF signaling pathways, having enhanced Fc effector functions, addressing drug resistance that can be mediated by the crosstalk amongst these three targets, as well as inhibiting angiogenesis. TAVO412 demonstrated strong <i>in vivo</i> tumor growth inhibition in 23 cell-line derived xenograft (CDX) models representing diverse cancer types, as well as in 9 patient-derived xenograft (PDX) lung tumor models.</p><p><strong>Methods: </strong>Using preclinical CDX data, we established transcriptomic biomarkers based on gene expression profiles that were correlated with anti-tumor response or distinguished between responders and non-responders. Together with specific driver mutation that associated with efficacy and the targets of TAVO412, a set of 21-gene biomarker was identified to predict the efficacy. A biomarker predictor was formulated based on the Linear Prediction Score (LPS) to estimate the probability of patients or tumor model response to TAVO412 treatment.</p><p><strong>Results: </strong>This efficacy predictor for TAVO412 demonstrated 78% accuracy in the CDX training models. The biomarker model was further validated in the PDX data set and resulted in comparable accuracy.</p><p><strong>Conclusions: </strong>In implementing precision medicine by leveraging preclinical model data, a predictive transcriptomic biomarker empowered by next-generation sequencing was identified that could optimize the selection of patients that may benefit most from TAVO412 treatment.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1505868"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Immunity and pulmonary vascular diseases: challenges, advances and future perspectives.","authors":"Qi Jin, Daxin Zhou, Zhihong Liu, Djuro Kosanovic","doi":"10.3389/fimmu.2025.1563584","DOIUrl":"10.3389/fimmu.2025.1563584","url":null,"abstract":"","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1563584"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of natural killer T and gammadelta T cells in mesothelin-targeted immunotherapy of pancreatic cancer.","authors":"Yuankui Zhu, Yaxi Yang, Linghe Yue, Lei Wan, Xuqian Ma, Qing Yang, Xuan Tian, Yuguan Li, Ke Wang, Shaozhong Wei, Dianbao Zuo, Mingqian Feng","doi":"10.3389/fimmu.2025.1524899","DOIUrl":"10.3389/fimmu.2025.1524899","url":null,"abstract":"<p><p>Current pancreatic cancer immunotherapy focused on alphabeta (αβ) T cells, either through CD3-engaged bispecific antibodies or CAR-T. Despite their promise, dose-limited toxicity (DLT) remains a challenge in clinical practice. In light of these concerns, there is a growing interest in exploring alternative T cell types, natural killer T (NKT) cells and gammadelta (γδ) T cells, that possess the capacity to lyse tumors while potentially offering a safer therapeutic profile with fewer side effects. These cells present a compelling alternative that warrants a comprehensive evaluation of their therapeutic potential and safety profile. This study employed a MSLN/CD3 bispecific antibody to compare the anti-tumor activity of NKT and γδT cells with peripheral blood mononuclear cells (PBMCs) as controls, both <i>in vitro</i> and <i>in vivo</i>. This study demonstrated that MSLN/CD3 BsAb effectively activated and recruited PBMCs, NKT and γδT. Furthermore, under the influence of MSLN/CD3 BsAb, γδT and NKT cells exhibited notably superior anti-tumor activity compared to PBMCs, both <i>in vitro</i> and <i>in vivo</i>, while demonstrating low cytokine release. γδT cells showed almost negligible toxic side effects. In addition, the systemic administration of NKT and γδT cells activators, α-galactosylceramide (α-GalCer) and Zoledronate, could enhance the anti-tumor effect of MSLN/CD3 bsAb, with no apparent toxicity. NKT and γδT cells are promising synergistic therapeutic cell types that may overcome the limitations of CD3 bispecific antibodies in pancreatic tumor treatments, offering a new perspective for clinical applications in immunotherapy.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1524899"},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}