Frontiers in ImmunologyPub Date : 2024-10-22eCollection Date: 2024-01-01DOI: 10.3389/fimmu.2024.1422784
Zhang Xuexian, Wang Ruidong, Ding Yuhan, Li Qingwei, Xiong Feng, Ren Hong, Zhang Jun, Li Wei
{"title":"Safety and efficacy of DEB-TACE in combination with lenvatinib and camrelizumab for the treatment of unresectable hepatocellular carcinoma (uHCC): a two-centre retrospective study.","authors":"Zhang Xuexian, Wang Ruidong, Ding Yuhan, Li Qingwei, Xiong Feng, Ren Hong, Zhang Jun, Li Wei","doi":"10.3389/fimmu.2024.1422784","DOIUrl":"10.3389/fimmu.2024.1422784","url":null,"abstract":"<p><strong>Objectives: </strong>The purpose of this study was to compare the safety and efficacy of drug-eluting bead (DEB) transarterial chemoembolization combined with lenvatinib and camrelizumab (DEB-TACE-Len-C) and DEB-TACE-Len for the treatment of unresectable hepatocellular carcinoma (uHCC).</p><p><strong>Methods: </strong>This retrospective study consecutively included uHCC patients who underwent DEB-TACE-Len-C or DEB-TACE-Len treatment at our hospital and Qujing Second People's Hospital from April 2020 to April 2022. In total, 85 patients were enrolled. There were 42 patients in the DEB-TACE-Len-C group and 43 patients in the DEB-TACE-Len group. The disease control rate (DCR), objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared between the two groups, and the factors influencing OS and PFS were analysed.</p><p><strong>Results: </strong>The ORR, DCR, PFS and OS were significantly greater in the DEB-TACE-Len-C group than in the DEB-TACE-Len group (ORR: 76.2% vs. 46.5%, <i>P</i> = 0.005; DCR: 88.1% vs. 67.8%, <i>P</i> = 0.039; PFS: 10 months vs. 6 months, <i>P <</i>0.0001; OS: 24 months vs. 16 months, <i>P</i> = 0.0038). Multivariate Cox proportional hazard regression analysis revealed that portal tumour thrombus (PVTT) and therapeutic approach were independent factors affecting PFS and OS. There were no statistically significant differences in the incidence of AEs between the two groups (<i>P</i> > 0.05).</p><p><strong>Conclusion: </strong>Compared with DEB-TACE-Len, DEB-TACE-Len-C is an effective treatment option that can improve the tumour therapeutic response and prolong the OS and PFS in uHCC patients.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582540","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}
Frontiers in ImmunologyPub Date : 2024-10-22eCollection Date: 2024-01-01DOI: 10.3389/fimmu.2024.1508462
Libia Alejandra Garcia-Flores, María Teresa Dawid De Vera, Jesus Pilo, Alejandro Rego, Gema Gomez-Casado, Isabel Arranz-Salas, Isabel Hierro Martín, Julia Alcaide, Esperanza Torres, Almudena Ortega-Gomez, Hatim Boughanem, Manuel Macias-Gonzalez
{"title":"Corrigendum: Increased neutrophil counts are associated with poor overall survival in patients with colorectal cancer: a five-year retrospective analysis.","authors":"Libia Alejandra Garcia-Flores, María Teresa Dawid De Vera, Jesus Pilo, Alejandro Rego, Gema Gomez-Casado, Isabel Arranz-Salas, Isabel Hierro Martín, Julia Alcaide, Esperanza Torres, Almudena Ortega-Gomez, Hatim Boughanem, Manuel Macias-Gonzalez","doi":"10.3389/fimmu.2024.1508462","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1508462","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fimmu.2024.1415804.].</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580804","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}
Frontiers in ImmunologyPub Date : 2024-10-22eCollection Date: 2024-01-01DOI: 10.3389/fimmu.2024.1478063
Brandon C Rosen, Kaitlin Sawatzki, Michael J Ricciardi, Elise Smith, Inah Golez, Jack T Mauter, Núria Pedreño-López, Aaron Yrizarry-Medina, Kim L Weisgrau, Logan J Vosler, Thomas B Voigt, Johan J Louw, Jennifer Tisoncik-Go, Leanne S Whitmore, Christakis Panayiotou, Noor Ghosh, Jessica R Furlott, Christopher L Parks, Ronald C Desrosiers, Jeffrey D Lifson, Eva G Rakasz, David I Watkins, Michael Gale
{"title":"Acute-phase innate immune responses in SIVmac239-infected <i>Mamu-B*08+</i> Indian rhesus macaques may contribute to the establishment of elite control.","authors":"Brandon C Rosen, Kaitlin Sawatzki, Michael J Ricciardi, Elise Smith, Inah Golez, Jack T Mauter, Núria Pedreño-López, Aaron Yrizarry-Medina, Kim L Weisgrau, Logan J Vosler, Thomas B Voigt, Johan J Louw, Jennifer Tisoncik-Go, Leanne S Whitmore, Christakis Panayiotou, Noor Ghosh, Jessica R Furlott, Christopher L Parks, Ronald C Desrosiers, Jeffrey D Lifson, Eva G Rakasz, David I Watkins, Michael Gale","doi":"10.3389/fimmu.2024.1478063","DOIUrl":"10.3389/fimmu.2024.1478063","url":null,"abstract":"<p><strong>Introduction: </strong>Spontaneous control of chronic-phase HIV/SIV viremia is often associated with the expression of specific MHC class I allotypes. HIV/SIV-specific CD8+ cytotoxic T lymphocytes (CTLs) restricted by these MHC class I allotypes appear to be critical for viremic control. Establishment of the elite controller (EC) phenotype is predictable in SIVmac239-infected Indian rhesus macaques (RMs), with approximately 50% of <i>Mamu-B*08</i>+ RMs and 20% of <i>Mamu-B*17</i>+ RMs becoming ECs. Despite extensive characterization of EC-associated CTLs in HIV/SIV-infected individuals, the precise mechanistic basis of elite control remains unknown. Because EC and non-EC viral load trajectories begin diverging by day 14 post-infection, we hypothesized that hyperacute innate immune responses may contribute to viremic control.</p><p><strong>Methods: </strong>To gain insight into the immunological factors involved in the determination of EC status, we vaccinated 16 <i>Mamu-B*08</i>+ RMs with Vif and Nef to elicit EC-associated CTLs, then subjected these 16 vaccinees and an additional 16 unvaccinated <i>Mamu-B*08</i>+ controls to repeated intrarectal SIVmac239 challenges. We then performed whole-blood transcriptomic analysis of all 32 SIVmac239-infected <i>Mamu-B*08</i>+ RMs and eight SIVmac239-infected <i>Mamu-B*08</i> <sup>-</sup> RMs during the first 14 days of infection.</p><p><strong>Results: </strong>Vaccination did not provide protection against acquisition, but peak and setpoint viremia were significantly lower in vaccinees relative to controls. We did not identify any meaningful correlations between vaccine-induced CTL parameters and SIVmac239 acquisition rate or chronic-phase viral loads. Ultimately, 13 of 16 vaccinees (81%) and 7 of 16 controls (44%) became ECs (viremia ≤ 10,000 vRNA copies/mL plasma for ≥ 4 weeks). We identified subsets of immunomodulatory genes differentially expressed (DE) between RM groupings based on vaccination status, EC status, and MHC class I genotype. These DE genes function in multiple innate immune processes, including the complement system, cytokine/chemokine signaling, pattern recognition receptors, and interferon-mediated responses.</p><p><strong>Discussion: </strong>A striking difference in the kinetics of differential gene expression among our RM groups suggests that <i>Mamu-B*08</i>-associated elite control is characterized by a robust, rapid innate immune response that quickly resolves. These findings indicate that, despite the association between MHC class I genotype and elite control, innate immune factors in hyperacute SIV infection preceding CTL response development may facilitate the establishment of the EC phenotype.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582298","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}
Frontiers in ImmunologyPub Date : 2024-10-22eCollection Date: 2024-01-01DOI: 10.3389/fimmu.2024.1500369
Laura A Dada, István Vadász
{"title":"Editorial: Endocytic and trafficking events in acute lung injury and pulmonary inflammation.","authors":"Laura A Dada, István Vadász","doi":"10.3389/fimmu.2024.1500369","DOIUrl":"10.3389/fimmu.2024.1500369","url":null,"abstract":"","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580805","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}
Frontiers in ImmunologyPub Date : 2024-10-22eCollection Date: 2024-01-01DOI: 10.3389/fimmu.2024.1433774
Bingjie Fu, Rui Liu, Gongzhizi Gao, Zujie Lin, Aili He
{"title":"Mechanisms and salvage treatments in patients with multiple myeloma relapsed post-BCMA CAR-T cell therapy.","authors":"Bingjie Fu, Rui Liu, Gongzhizi Gao, Zujie Lin, Aili He","doi":"10.3389/fimmu.2024.1433774","DOIUrl":"10.3389/fimmu.2024.1433774","url":null,"abstract":"<p><p>Chimeric antigen receptor T-cell (CAR-T) therapy has ushered in a new era for the treatment of multiple myeloma (MM). Numerous clinical studies, especially those involving B-cell maturation antigen (BCMA)-directed CAR-T, have shown remarkable efficacy in patients with relapsed or refractory multiple myeloma (R/R MM). However, a considerable number of patients still experience disease recurrence or progression after BCMA CAR-T treatment, which is attributed to various factors, including antigen escape, CAR-T manufacturing factors, T cell exhaustion, inhibitory effects of tumor microenvironment and impact of prior treatments. The scarcity of effective treatment options following post-CAR-T disease recurrence, coupled with the lack of well-established salvage regimens, leaves patients who do relapse facing a bleak prognosis. In recent years, some academic institutions have achieved certain results in salvage treatments of patients with relapse after BCMA CAR-T treatment through secondary infusion of BCMA CAR-T, changing to non-BCMA-directed CAR-T, double-target CAR-T, bispecific antibodies or other novel therapies. This review summarizes the mechanisms of resistance or relapse after BCMA CAR-T administration and the available data on current salvage treatments, hoping to provide ideas for optimizing clinical salvage therapies.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582550","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}
Frontiers in ImmunologyPub Date : 2024-10-22eCollection Date: 2024-01-01DOI: 10.3389/fimmu.2024.1451356
Young Joo Han, SungSu Kim, Haksup Shin, Hyun Woo Kim, June Dong Park
{"title":"Protective effect of gut microbiota restored by fecal microbiota transplantation in a sepsis model in juvenile mice.","authors":"Young Joo Han, SungSu Kim, Haksup Shin, Hyun Woo Kim, June Dong Park","doi":"10.3389/fimmu.2024.1451356","DOIUrl":"10.3389/fimmu.2024.1451356","url":null,"abstract":"<p><strong>Introduction: </strong>Restoring a balanced, healthy gut microbiota through fecal microbiota transplantation (FMT) has the potential to be a treatment option for sepsis, despite the current lack of evidence. This study aimed to investigate the effect of FMT on sepsis in relation to the gut microbiota through a sepsis model in juvenile mice.</p><p><strong>Methods: </strong>Three-week-old male mice were divided into three groups: the antibiotic treatment (ABX), ABX-FMT, and control groups. The ABX and ABX-FMT groups received antibiotics for seven days. FMT was performed through oral gavage in the ABX-FMT group over the subsequent seven days. On day 14, all mice underwent cecal ligation and puncture (CLP) to induce abdominal sepsis. Blood cytokine levels and the composition of fecal microbiota were analyzed, and survival was monitored for seven days post-CLP.</p><p><strong>Results: </strong>Initially, the fecal microbiota was predominantly composed of the phyla Bacteroidetes and Firmicutes. After antibiotic intake, an extreme predominance of the class Bacilli emerged. FMT successfully restored antibiotic-induced fecal dysbiosis. After CLP, the phylum Bacteroidetes became extremely dominant in the ABX-FMT and control groups. Alpha diversity of the microbiota decreased after antibiotic intake, was restored after FMT, and decreased again following CLP. In the ABX group, the concentrations of interleukin-1β (IL-1β), IL-2, IL-6, IL-10, granulocyte macrophage colony-stimulating factor, tumor necrosis factor-α, and C-X-C motif chemokine ligand 1 increased more rapidly and to a higher degree compared to other groups. The survival rate in the ABX group was significantly lower (20.0%) compared to other groups (85.7%).</p><p><strong>Conclusion: </strong>FMT-induced microbiota restoration demonstrated a protective effect against sepsis. This study uniquely validates the effectiveness of FMT in a juvenile mouse sepsis model, offering potential implications for clinical research in critically ill children.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582538","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}
Frontiers in ImmunologyPub Date : 2024-10-22eCollection Date: 2024-01-01DOI: 10.3389/fimmu.2024.1473133
Olivia C Ihedioha, Haley Q Marcarian, Anutr Sivakoses, Stephen M Beverley, Diane McMahon-Pratt, Alfred L M Bothwell
{"title":"<i>Leishmania major</i> surface components and DKK1 signalling via LRP6 promote migration and longevity of neutrophils in the infection site.","authors":"Olivia C Ihedioha, Haley Q Marcarian, Anutr Sivakoses, Stephen M Beverley, Diane McMahon-Pratt, Alfred L M Bothwell","doi":"10.3389/fimmu.2024.1473133","DOIUrl":"10.3389/fimmu.2024.1473133","url":null,"abstract":"<p><strong>Background: </strong>Host-related factors highly regulate the increased circulation of neutrophils during <i>Leishmania</i> infection. Platelet-derived Dickkopf-1 (DKK1) is established as a high-affinity ligand to LRP6. Recently, we demonstrated that DKK1 upregulates leukocyte-platelet aggregation, infiltration of neutrophils to the draining lymph node and Th2 differentiation during <i>Leishmania</i> infection, suggesting the potential involvement of the DKK1-LRP6 signalling pathway in neutrophil migration in infectious diseases.</p><p><strong>Results: </strong>In this study, we further explored the potential role of DKK1-LRP6 signalling in the migration and longevity of activated neutrophils in the infection site using BALB/c mice with PMNs deficient in LRP6 (LRP6<sup>NKO</sup>) or BALB/c mice deficient in both PMN LRP6 and platelet DKK1 (LRP6<sup>NKO</sup> DKK1<sup>PKO</sup>). Relative to the infected wild-type BALB/c mice, reduced neutrophil activation at the infection site of LRP6<sup>NKO</sup> or LRP6<sup>NKO</sup> DKK1<sup>PKO</sup> mice was noted. The neutrophils obtained from either infected LRP6<sup>NKO</sup> or LRP6<sup>NKO</sup> DKK1<sup>PKO</sup> mice additionally showed a high level of apoptosis. Notably, the level of LRP6 expressing neutrophils was elevated in infected BALB/c mice. Relative to infected BALB/c mice, a significant reduction in parasite load was observed in both LRP6<sup>NKO</sup> and LRP6<sup>NKO</sup> DKK1<sup>PKO</sup> infected mice. Notably, DKK1 levels were comparable in the LRP6<sup>NKO</sup> and BALB/c mice in response to infection, indicating that PMN activation is the major pathway for DKK1 in promoting parasitemia. Parasite-specific components also play a crucial role in modulating neutrophil circulation in <i>Leishmania</i> disease. Thus, we further determine the contribution of <i>Leishmania</i> membrane components in the migration of neutrophils to the infection site using null mutants deficient in LPG synthesis (<i>Δlpg1<sup>-</sup></i> ) or lacking all ether phospholipids (plasmalogens, LPG, and GIPLs) synthesis (<i>Δads1<sup>-</sup></i> ). Relative to the WT controls, <i>Δads1<sup>-</sup></i> parasite-infected mice showed a sustained decrease in neutrophils and neutrophil-platelet aggregates (for at least 14 days PI), while neutrophils returned to normal in <i>Δlpg1<sup>-</sup></i> parasite-infected mice after day 3 PI.</p><p><strong>Conclusion: </strong>Our results suggest that DKK1 signalling and <i>Leishmania</i> pathogen-associated molecular patterns appear to regulate the migration and sustenance of viable activated neutrophils in the infection site resulting in chronic type 2 cell-mediated inflammation.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582189","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}
Frontiers in ImmunologyPub Date : 2024-10-22eCollection Date: 2024-01-01DOI: 10.3389/fimmu.2024.1461361
Liesbet M Peeters
{"title":"The arisal of data spaces: why I am excited and worried.","authors":"Liesbet M Peeters","doi":"10.3389/fimmu.2024.1461361","DOIUrl":"10.3389/fimmu.2024.1461361","url":null,"abstract":"<p><p>This paper explores the significant role of real-world data (RWD) in advancing our understanding and management of Multiple Sclerosis (MS). RWD has proven invaluable in MS research and care, offering insights from larger and diverse patient populations. A key focus of the paper is the European Health Data Space (EHDS), a significant development that promises to change how healthcare data is managed across Europe. This initiative is particularly relevant to the MS community. The paper highlights various data initiatives, discussing their importance for those affected by MS. Despite the potential benefits, there are challenges and concerns, especially about ensuring that the growth of various data platforms remains beneficial for MS patients. The paper suggests practical actions for the global MS community to consider, aimed at optimizing the use of RWD. The emphasis of this discussion is on the secondary use of health data, particularly in the European context. The content is based on the author's own experiences and interpretations, offering a personal yet informed view on using RWD to improve MS research and patient care.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582555","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":"Comprehensive analysis of VEGF/VEGFR inhibitor-induced immune-mediated hypertension: integrating pharmacovigilance, clinical data, and preclinical models.","authors":"Hongyu Kuang, Qingkai Yan, Zhanzhi Li, Anqi Lin, Kailai Li, Jian Zhang, Peng Luo, Yuehui Yin","doi":"10.3389/fimmu.2024.1488853","DOIUrl":"10.3389/fimmu.2024.1488853","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to elucidate the differential immunological mechanisms and characteristics of hypertension induced by VEGF inhibitors (VEGFi) and VEGF receptor inhibitors (VEGFRi), with the goal of optimizing monitoring strategies and treatment protocols.</p><p><strong>Methods: </strong>We investigated the risk of immune-related adverse events associated with VEGFi/VEGFRi-induced hypertension by analyzing the FDA Adverse Event Reporting System (FAERS) database. Findings were corroborated with blood pressure characteristics observed in clinical patients and preclinical models exposed to various VEGF/VEGFRi. Clinical and preclinical studies were conducted to compare immunological responses and hypertension profiles between inhibitor classes. An integrative analysis across cancer types and species was performed, focusing on key signaling pathways.</p><p><strong>Results: </strong>Analysis of FAERS data, in conjunction with clinical observations, revealed that both VEGFi and VEGFRi significantly elevated the risk of immune-mediated, blood pressure-related adverse events (ROR=7.75, 95% CI: 7.76-7.95). Subsequent clinical and preclinical studies demonstrated differential immunological responses and hypertension profiles between inhibitor classes. VEGFRi exhibited a more rapid onset, greater blood pressure elevation, and higher incidence of immune-mediated adverse events compared to VEGFi (Systolic BP: ROR=0 for VEGFi vs. ROR=12.25, 95% CI: 6.54-22.96 for VEGFRi; Diastolic BP: ROR=5.09, 95% CI: 0.60-43.61 for VEGFi vs. ROR=12.90, 95% CI: 3.73-44.55 for VEGFRi). Integrative analysis across cancer types and species, focusing on key signaling pathways, revealed that VEGF/VEGFRi-induced blood pressure elevation was associated with immunomodulation of the mitogen activated protein kinase (MAPK) pathway (R=-0.379, P=0.0435), alterations in triglyceride metabolism (R=-0.664, P=0.0001), modulation of myo-inositol 1,4,5-trisphosphate-sensitive calcium release channel activity (R=0.389, P=0.0378), and dysregulation of nitric oxide eNOS activation and metabolism (R=-0.439, P=0.0179).</p><p><strong>Discussion: </strong>The temporal dynamics of these effects demonstrated greater significance than dose-dependent responses. Both VEGFi and VEGFRi significantly augmented the risk of immune-mediated, blood pressure-related adverse events, with VEGFRi inducing a more rapid and pronounced onset of blood pressure elevation and a higher incidence of immune-related, blood pressure-associated adverse events compared to VEGFi.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582373","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}
Frontiers in ImmunologyPub Date : 2024-10-22eCollection Date: 2024-01-01DOI: 10.3389/fimmu.2024.1477130
Yanli Yang, Yang Liu, Yu Chen, Di Luo, Ke Xu, Liyun Zhang
{"title":"Artificial intelligence for predicting treatment responses in autoimmune rheumatic diseases: advancements, challenges, and future perspectives.","authors":"Yanli Yang, Yang Liu, Yu Chen, Di Luo, Ke Xu, Liyun Zhang","doi":"10.3389/fimmu.2024.1477130","DOIUrl":"10.3389/fimmu.2024.1477130","url":null,"abstract":"<p><p>Autoimmune rheumatic diseases (ARD) present a significant global health challenge characterized by a rising prevalence. These highly heterogeneous diseases involve complex pathophysiological mechanisms, leading to variable treatment efficacies across individuals. This variability underscores the need for personalized and precise treatment strategies. Traditionally, clinical practices have depended on empirical treatment selection, which often results in delays in effective disease management and can cause irreversible damage to multiple organs. Such delays significantly affect patient quality of life and prognosis. Artificial intelligence (AI) has recently emerged as a transformative tool in rheumatology, offering new insights and methodologies. Current research explores AI's capabilities in diagnosing diseases, stratifying risks, assessing prognoses, and predicting treatment responses in ARD. These developments in AI offer the potential for more precise and targeted treatment strategies, fostering optimism for enhanced patient outcomes. This paper critically reviews the latest AI advancements for predicting treatment responses in ARD, highlights the current state of the art, identifies ongoing challenges, and proposes directions for future research. By capitalizing on AI's capabilities, researchers and clinicians are poised to develop more personalized and effective interventions, improving care and outcomes for patients with ARD.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582399","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}