Frontiers in Immunology最新文献

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Recurrent reproductive failure and celiac genetic susceptibility, a leading role of gluten. 复发性生殖系统衰竭与乳糜泻遗传易感性,麸质蛋白起主导作用。
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1451552
Eduardo de la Fuente-Munoz, Miguel Fernández-Arquero, Nabil Subbhi-Issa, Kissy Guevara-Hoyer, Lydia Pilar Suárez, Raquel Gil Laborda, Marina Sánchez, Juliana Ochoa-Grullón, María Guzmán-Fulgencio, Ángela Villegas, María Dolores Mansilla, Noelia Pérez, Ricardo Savirón Cornudella, Teresa Gastañaga-Holguera, Marta Calvo Urrutia, Ignacio Cristóbal García, Silvia Sánchez-Ramón
{"title":"Recurrent reproductive failure and celiac genetic susceptibility, a leading role of gluten.","authors":"Eduardo de la Fuente-Munoz, Miguel Fernández-Arquero, Nabil Subbhi-Issa, Kissy Guevara-Hoyer, Lydia Pilar Suárez, Raquel Gil Laborda, Marina Sánchez, Juliana Ochoa-Grullón, María Guzmán-Fulgencio, Ángela Villegas, María Dolores Mansilla, Noelia Pérez, Ricardo Savirón Cornudella, Teresa Gastañaga-Holguera, Marta Calvo Urrutia, Ignacio Cristóbal García, Silvia Sánchez-Ramón","doi":"10.3389/fimmu.2024.1451552","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1451552","url":null,"abstract":"<p><strong>Introduction: </strong>The prevalence of gluten-related disorders, mainly celiac disease (CD) and non-celiac gluten sensitivity (NCGS), varies between 0.6% and 13% in the general population. There is controversial evidence regarding the association of both CD and NCGS with extra-digestive manifestations, including recurrent reproductive failure (RRF), which may have clinical implications.</p><p><strong>Objective: </strong>To study the prevalence of HLA susceptibility alleles for CD/NCGS in a cohort of female patients with RRF from a single reference center and to evaluate the effect of a gluten-free diet on reproductive success.</p><p><strong>Material and methods: </strong>A retrospective study was conducted on 173 patients with RRF, consecutively attended at the Reproductive Immunology Unit of San Carlos University Clinical Hospital in Madrid. We collected and analyzed the clinical, analytical, and immunological profiles of RRF patients who presented HLA alleles associated with CD and NCGS (HLA DQ2.2, DQ2.5, DQ8, and DQ7.5).</p><p><strong>Results: </strong>We observed a significantly higher prevalence of HLA alleles associated with CD and NCGS in our RRF cohort compared to the prevalence in the general population (69% vs. 35%-40%, p<0.0001). Only 2.3% of patients met the criteria for a CD diagnosis. In our RRF cohort, HLA-genetic susceptibility for CD/NCGS (HLA-risk group) was associated with a significantly higher rate of hypothyroidism compared to patients without these alleles (HLA-negative group) (48.7% vs. 26.92%, p=0.03). Patients with HLA-genetic susceptibility for CD/NCGS and thyroid disease had a significantly higher success rate in the subsequent pregnancy after management (55% vs. 30%, p=0.002). Two factors were found to be significant in this group: a gluten-free diet (p=0.019) and the use of levothyroxine (p=0.042).</p><p><strong>Conclusions: </strong>In our cohort of RRF patients, we observed a significantly higher prevalence of HLA susceptibility genes for CD/NCGS compared to the general population, also associated with a higher incidence of thyroid alterations. A gluten-free diet and the use of levothyroxine in cases of thyroid pathology had significant beneficial effects on pregnancy outcomes. We suggest that HLA typing for CD/NCGS and a gluten-free diet, in the presence of risk alleles, can improve pregnancy outcomes in RRF patients.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603910","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}
引用次数: 0
Glycosylation signature of plasma IgA of critically ill COVID-19 patients. COVID-19 重症患者血浆 IgA 的糖基化特征。
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1439248
Daniel P Potaczek, Bianca D M van Tol, David Falck, Christina Krolczik, Kristina Zlatina, Wilhelm Bertrams, Jochen Wilhelm, Bernd Schmeck, Benjamin Seeliger, Sascha David, Chrysanthi Skevaki, Elisabeth Mack, Werner Seeger, Liliana Schaefer, Sebastian P Galuska, Manfred Wuhrer, Małgorzata Wygrecka
{"title":"Glycosylation signature of plasma IgA of critically ill COVID-19 patients.","authors":"Daniel P Potaczek, Bianca D M van Tol, David Falck, Christina Krolczik, Kristina Zlatina, Wilhelm Bertrams, Jochen Wilhelm, Bernd Schmeck, Benjamin Seeliger, Sascha David, Chrysanthi Skevaki, Elisabeth Mack, Werner Seeger, Liliana Schaefer, Sebastian P Galuska, Manfred Wuhrer, Małgorzata Wygrecka","doi":"10.3389/fimmu.2024.1439248","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1439248","url":null,"abstract":"<p><p>Thromboembolic complications are common in severe COVID-19 and are thought to result from excessive neutrophil-extracellular-trap (NET)-driven immunothrombosis. Glycosylation plays a vital role in the efficiency of immunoglobulin A (IgA) effector functions, with significant implications for NET formation in infectious diseases. This study represents the first comprehensive analysis of plasma IgA glycosylation during severe SARS-CoV-2 or Influenza A infection, revealing lower sialylation and higher galactosylation of IgA1 O-glycans in acute respiratory distress syndrome (ARDS), regardless of the underlying cause of the disease. Importantly, N-glycans displayed an infection-specific pattern, with N47 of IgA2 showing diminished sialylation and bisection, and N340/N327 of IgA1/2 demonstrating lower fucosylation and antennarity along with higher non-complex glycans in COVID-19 compared to Influenza. Notably, COVID-19 IgA possessed strong ability to induce NET formation and its glycosylation patterns correlated with extracellular DNA levels in plasma of critically ill COVID-19 patients. Our data underscores the necessity of further research on the role of IgA glycosylation in the modulation of pathogen-specific immune responses in COVID-19 and other infectious diseases.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603504","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}
引用次数: 0
Case report: A rare EBV-associated T/NK cell monomorphic posttransplant lymphoproliferative disorder. 病例报告:一种罕见的 EBV 相关 T/NK 细胞单形性移植后淋巴组织增生性疾病。
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1491681
Xin Jiang, Yao-Yu Zhang, Xiao-Wei Li, Xiao-Dong Li, Zhan-Yuan Li, Wen-Jun Meng, Sha-Dan Li
{"title":"Case report: A rare EBV-associated T/NK cell monomorphic posttransplant lymphoproliferative disorder.","authors":"Xin Jiang, Yao-Yu Zhang, Xiao-Wei Li, Xiao-Dong Li, Zhan-Yuan Li, Wen-Jun Meng, Sha-Dan Li","doi":"10.3389/fimmu.2024.1491681","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1491681","url":null,"abstract":"<p><strong>Background: </strong>Kidney transplantation (KT) is the best treatment for patients with end-stage renal disease. However, postoperative complications remain the main issues faced during KT recovery period. Posttransplant lymphoproliferative disorders (PTLD) are one of the severe and life-threatening complications that occur after KT while the recipient is undergoing immunosuppressive therapy. PTLD risk factors include Epstein-Barr virus (EBV) infection, the cumulative degree of immunosuppression, as well as genetic aspects. PTLD is more common in the transplanted organ itself and its surroundings, and the central nervous system, while PTLD involving the pharyngeal soft tissue is relatively rare, with only a few reported case reports. Therefore, systematic experience is scarce regarding whether the treatment or the care.</p><p><strong>Case presentation: </strong>Herein, we report a 41-year-old male, underwent a reproductive KT due to chronic renal insufficiency. Recurrent fever, pharyngeal pain, and bilateral cervical lymph node enlargement were recurred during five years' follow-up after KT surgery. In this inpatient experience, the patient vomited a large amount of blood from the oropharynx, then the tonsil artery was ligated by emergency operation. EBV-associated T/NK cell monomorphic PTLD was eventually diagnosed by blood EBV DNA test, pharyngeal biopsy, and corresponding pathological examination. After six cycles of R-CHOP chemotherapy, the clinical symptoms and laboratory tests changed into normal. Subsequent three years' follow-up shows no tumor recurrence and good transplant kidney function.</p><p><strong>Conclusion: </strong>This rare case report describes a manifestation of PTLD with pharyngeal involvement. Early diagnosis using histopathological examination is crucial to prevent damage to the throat and airway, and even life-threatening conditions. Discontinuing immunosuppression and starting systemic treatment can help in disease regression. Since the low incidence of this disease, limited clinical experience, and limited data, our experience with a smooth recovery through efficacy treatment and nursing can provide a reference for the development of new clinical drugs and diagnostic and treatment plans of patients with PTLD in the future.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602225","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}
引用次数: 0
Epstein-Barr virus-specific T-cell response in pediatric liver transplant recipients: a cross-sectional study by multiparametric flow cytometry. 小儿肝移植受者的 Epstein-Barr 病毒特异性 T 细胞反应:多参数流式细胞术横断面研究。
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1479472
Ricardo Cuesta-Martín de la Cámara, Andrea Torices-Pajares, Laura Miguel-Berenguel, Keren Reche-Yebra, Esteban Frauca-Remacha, Loreto Hierro-Llanillo, Gema Muñoz-Bartolo, María Dolores Lledín-Barbacho, Almudena Gutiérrez-Arroyo, Ana Martínez-Feito, Eduardo López-Granados, Elena Sánchez-Zapardiel
{"title":"Epstein-Barr virus-specific T-cell response in pediatric liver transplant recipients: a cross-sectional study by multiparametric flow cytometry.","authors":"Ricardo Cuesta-Martín de la Cámara, Andrea Torices-Pajares, Laura Miguel-Berenguel, Keren Reche-Yebra, Esteban Frauca-Remacha, Loreto Hierro-Llanillo, Gema Muñoz-Bartolo, María Dolores Lledín-Barbacho, Almudena Gutiérrez-Arroyo, Ana Martínez-Feito, Eduardo López-Granados, Elena Sánchez-Zapardiel","doi":"10.3389/fimmu.2024.1479472","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1479472","url":null,"abstract":"<p><strong>Background: </strong>Epstein-Barr virus (EBV) specific T-cell response measurement can help adjust immunosuppression in transplant patients with persistent infections. We aim to define T-cell responses against EBV in a cohort of pediatric liver-transplant patients.</p><p><strong>Methods: </strong>Thirty-eight immunosuppressed pediatric liver-transplant patients (IP) and 25 EBV-seropositive healthy-adult controls (HC) were included in our cross-sectional study. Based on their EBV serological (S) and viral load (VL) status, patients were categorized into IP-S<sup>NEG</sup>, IP-S<sup>POS</sup>VL<sup>NEG</sup> and IP-S<sup>POS</sup>VL<sup>POS</sup> groups. T-cell response was assessed at two timepoints by stimulating cells with EBV peptides (PepTivator<sup>®</sup>) and performing intracellular-cytokine and activation-induced marker staining. Background subtraction was used to determine EBV-specific T-lymphocyte frequency.</p><p><strong>Results: </strong>Polyfunctional CD8+ T cells indicated previous EBV contact (IP-S<sup>NEG</sup> 0.00% vs IP-S<sup>POS</sup> 0.04% and HC 0.02%; p=0.001 and p=0.01, respectively). Polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- profile was increased in serology-positive (IP-S<sup>NEG</sup> 0.01% vs IP-S<sub>POS</sub> 0.13% and HC 0.03%; p=0.01 and p=0.50, respectively) and viral-load positive (IP-S<sup>POS</sup>VL<sup>POS</sup> 0.43% vs IP-S<sup>POS</sup>VL<sup>NEG</sup> 0.07% and HC 0.03%; p=0.03 and p=0.001, respectively) patients. Central-memory cells were increased among serology-positive adults (IP-S<sup>NEG</sup> 0.00% vs IP-S<sup>POS</sup> 0.13% and HC 4.33%; p=0.58 and p=0.002, respectively). At the second timepoint, IP-S<sup>NEG</sup> patients remained negative (first visit 0.01% vs second visit 0.00%, p=0.44). On the other hand, IP-S<sup>POS</sup>VL<sup>POS</sup> patients had cleared viral loads and, subsequently, decreased polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- cells (first visit 0.43% vs second visit 0.10%, p=0.81).</p><p><strong>Conclusion: </strong>Polyfunctional CD8+ EBV-specific T-cell response allows detecting EBV previous contact in liver-transplant children. %CD8+CD107a+IFNɣ+IL2-TNFα- is increased in patients with positive viral loads. Central memory CD4+ T-cell population more effectively determines prior EBV-exposure in adults.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603501","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}
引用次数: 0
Genetically modified and unmodified cellular approaches to enhance graft versus leukemia effect, without increasing graft versus host disease: the use of allogeneic cytokine-induced killer cells. 基因修饰和未修饰的细胞方法,在不增加移植物对宿主疾病的情况下增强移植物对白血病的疗效:使用异体细胞因子诱导的杀伤细胞。
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1459175
Benedetta Rambaldi, Giuliana Rizzuto, Alessandro Rambaldi, Martino Introna
{"title":"Genetically modified and unmodified cellular approaches to enhance graft versus leukemia effect, without increasing graft versus host disease: the use of allogeneic cytokine-induced killer cells.","authors":"Benedetta Rambaldi, Giuliana Rizzuto, Alessandro Rambaldi, Martino Introna","doi":"10.3389/fimmu.2024.1459175","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1459175","url":null,"abstract":"<p><p>Although allogeneic hematopoietic cell transplantation (HCT) represents a curative approach for many patients with hematological diseases, post-transplantation relapse occurs in 20-50% of cases, representing the primary cause of treatment failure and mortality. Alloreactive donor T cells are responsible for the graft versus leukemia (GvL) effect, which represents the key mechanism for the long-term curative effect of HCT. However, the downside is represented by graft versus host disease (GvHD), largely contributing to transplant-related mortality (TRM). Multiple factors play a role in regulating the delicate balance between GvL and GvHD, such as the optimization of the donor HLA and KIR match, the type of graft source, and the adaptive use of post-transplant cellular therapy. In addition to the standard donor lymphocyte infusion (DLI), several attempts were made to favor the GvL effect without increasing the GvHD risk. Selected DLI, NK DLI, activated DLI and more sophisticated genetically engineered cells can be employed. In this scenario, cytokine-induced killer (CIK) cells represent a suitable tool to boost GvL while minimizing GvHD. CIK cells are T lymphocytes activated in culture in the presence of monoclonal antibodies against CD3 (OKT3), interferon-gamma (IFN-g), and interleukin-2 (IL-2), characterized by the expression of markers typical of NK cells and T cells (CD3<sup>+</sup>, CD56<sup>+</sup>, with a prevalent CD8<sup>+</sup> phenotype). CIK cells can mediate cytotoxicity through both MHC and non-MHC restricted recognition, which is the so-called \"dual-functional capability\" and display minimum alloreactivity. Allogeneic CIK cells showed a favorable rate of response, especially in the setting of minimal residual disease, with a rate of GvHD not exceeding 25%. Finally, the CIK cell platform can be adapted for chimeric antigen receptor (CAR) cell strategy, showing promising results in both preclinical and clinical settings. In this review, we describe the main immunological basis for the development of the GvL and the possible cellular therapy approaches used to boost it, with a particular focus on the use of CIK cells.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603502","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}
引用次数: 0
Sarcomatoid carcinoma transformation in oral undifferentiated carcinoma following sequential immune combined targeted therapy: a case report. 口腔未分化癌在连续免疫联合靶向治疗后发生肉瘤样癌转化:病例报告。
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1484915
Jieying Li, Xiaohong Zhan, Wei Shang, Kai Song
{"title":"Sarcomatoid carcinoma transformation in oral undifferentiated carcinoma following sequential immune combined targeted therapy: a case report.","authors":"Jieying Li, Xiaohong Zhan, Wei Shang, Kai Song","doi":"10.3389/fimmu.2024.1484915","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1484915","url":null,"abstract":"<p><p>The diagnosis and treatment of head and neck undifferentiated carcinoma (HNUC) present significant challenges. Herein, we present the case of a patient with advanced HNUC who underwent conversion surgery following treatment with a combination of pembrolizumab and nimotuzumab. During therapy, histological transformation from undifferentiated to sarcomatoid carcinoma was detected at the primary site. This case not only highlights the potential of immune combination-targeted therapy to reduce tumour burden and increase the surgical options for patients, but also reveals the complex alterations in tumour biology that may occur during treatment. It emphasizes the necessity for routine pathological assessments throughout the therapeutic regimen to guide personalised therapeutic strategies and optimise patient prognoses.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603876","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}
引用次数: 0
Effect of peripheral blood lymphocyte count on the efficacy of immunotherapy combined with TKI in the treatment of advanced liver cancer. 外周血淋巴细胞计数对免疫疗法联合 TKI 治疗晚期肝癌疗效的影响。
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1467429
Qian Zhao, Lei Wang, Huilan Fu, Yuqin Zhang, Qiankun Xie
{"title":"Effect of peripheral blood lymphocyte count on the efficacy of immunotherapy combined with TKI in the treatment of advanced liver cancer.","authors":"Qian Zhao, Lei Wang, Huilan Fu, Yuqin Zhang, Qiankun Xie","doi":"10.3389/fimmu.2024.1467429","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1467429","url":null,"abstract":"<p><strong>Background and aims: </strong>Compared with tyrosine kinase inhibitor (TKI) monotherapy, TKI combined with PD1 can improve the therapeutic effect of liver cancer and has been widely used in clinical practice. However, there is a lack of effective biomarkers to identify patients who would benefit more from this combination therapy. Therefore, this study aimed to evaluate whether baseline lymphocyte counts can identify patients with liver cancer who would benefit from targeted immune combination therapy.</p><p><strong>Methods: </strong>Data from patients with hepatocellular carcinoma (HCC) who received TKIs or TKIs in combination with PD1 between June 2018 and June 2020 were retrospectively collected. The patients were divided into high and low groups based on the median absolute count of peripheral lymphocytes before systemic therapy and differences in overall survival (OS) and progression-free survival (PFS) between TKI and TKI+PD1 were compared between the two groups.</p><p><strong>Results: </strong>In total, 72 patients were included in this study, with a median follow-up of 1.5 years. Both PFS and OS in the TKI+PD1 group showed a good prognostic trend (p = 0.058 and p = 0.077, respectively). Subgroup analyses based on peripheral blood lymphocyte counts showed that the combination regimen had a significant PFS and OS advantage only in patients with high peripheral blood lymphocyte counts (p = 0.036 and p = 0.031, respectively), but not in patients with low absolute peripheral blood lymphocyte counts (p = 0.819 and p = 0.913, respectively).</p><p><strong>Conclusions: </strong>Peripheral blood lymphocyte count is a simple and effective biomarker that can be used to identify patients with liver cancer who will benefit more from TKI+PD-1 combination therapy.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603298","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}
引用次数: 0
Analysis of the treatment efficacy and prognostic factors of PD-1/PD-L1 inhibitors for advanced gastric or gastroesophageal junction cancer: a multicenter, retrospective clinical study. PD-1/PD-L1抑制剂治疗晚期胃癌或胃食管交界癌的疗效和预后因素分析:一项多中心回顾性临床研究。
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1468342
Yuanyuan Yang, Zhe Wang, Dao Xin, Lulu Guan, Bingtong Yue, Qifan Zhang, Feng Wang
{"title":"Analysis of the treatment efficacy and prognostic factors of PD-1/PD-L1 inhibitors for advanced gastric or gastroesophageal junction cancer: a multicenter, retrospective clinical study.","authors":"Yuanyuan Yang, Zhe Wang, Dao Xin, Lulu Guan, Bingtong Yue, Qifan Zhang, Feng Wang","doi":"10.3389/fimmu.2024.1468342","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1468342","url":null,"abstract":"<p><strong>Introduction: </strong>Immune checkpoint inhibitors (ICIs) have transformed advanced gastric cancer treatment, yet patient responses vary, highlighting the need for effective biomarkers. Common markers, such as programmed cell death ligand-1 (PD-L1), microsatellite instability/mismatch repair (MSI/MMR), tumor mutational burden, tumor-infiltrating lymphocytes, and Epstein-Barr virus, face sampling challenges and high costs. This study seeks practical, minimally invasive biomarkers to enhance patient selection and improve outcomes.</p><p><strong>Methods: </strong>This multicenter retrospective study analyzed 617 patients with advanced gastric or gastroesophageal junction cancer treated with programmed cell death protein-1 (PD-1)/PD-L1 inhibitors from January 2019 to March 2023. Clinical data and peripheral blood marker data were collected before and after treatment. The primary endpoints were overall survival (OS) and progression-free survival (PFS); the secondary endpoints included the objective response rate (ORR) and disease control rate (DCR). Least absolute shrinkage and selection operator (LASSO)-Cox and LASSO logistic regression analyses identified independent factors for OS, PFS, and ORR. Predictive nomograms were validated using receiver operating characteristic (ROC) curves, areas under the curve (AUCs), C-indices, and calibration curves, with clinical utility assessed via decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI).</p><p><strong>Results: </strong>OS-related factors included treatment line, T stage, ascites, pretreatment indirect bilirubin (pre-IBIL), posttreatment CA125, CA199, CA724, and the PLR. PFS-related factors included treatment lines, T stage, metastatic sites, pre-IBIL, posttreatment globulin (GLOB), CA125, and CA199 changes. ORR-related factors included treatment line, T stage, N stage, liver metastasis, pretreatment red cell distribution width-to-platelet ratio (RPR), CA125, and CA724 changes. The nomograms showed strong predictive performance and clinical utility.</p><p><strong>Conclusions: </strong>Early treatment, lower T stage, the absence of ascites, and lower pre-IBIL, post-CA125, CA199, CA724, and PLR correlate with better OS. Factors for improved PFS include early treatment, lower T stage, fewer metastatic sites, and lower pre-IBIL, post-GLOB, and post-CA125 levels. Nomogram models can help identify patients who may benefit from immunotherapy, providing valuable clinical guidance.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602051","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}
引用次数: 0
Awareness, knowledge, and beliefs about probiotics and prebiotics among Saudi adults: a cross-sectional study. 沙特成年人对益生菌和益生元的认识、知识和信念:一项横断面研究。
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1464622
Areej Ali Alkhaldy
{"title":"Awareness, knowledge, and beliefs about probiotics and prebiotics among Saudi adults: a cross-sectional study.","authors":"Areej Ali Alkhaldy","doi":"10.3389/fimmu.2024.1464622","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1464622","url":null,"abstract":"<p><strong>Background: </strong>Probiotics and Prebiotics are essential for supporting both overall health and gastrointestinal health. However, the perception of these dietary components among the general public in Saudi Arabia is not well understood. The purpose of this study was to evaluate public awareness, knowledge, and beliefs regarding prebiotics and probiotics across Saudi Arabia.</p><p><strong>Materials and methods: </strong>Our cross-sectional study included 1,306 participants aged 18 years and above. Data were collected in Saudi Arabia between May and July 2023 using a self-administered online questionnaire via convenience sampling.</p><p><strong>Results: </strong>A high level of awareness was self-reported by only 21.9% of participants, whereas more than half (51.8%) of participants rated their level of awareness as low. Overall, 37.5% of participants displayed a high level of knowledge about probiotics and prebiotics, whereas 15.5% had a low level of knowledge. The majority of participants believed in the beneficial effects of probiotics and prebiotics on overall digestion/gut health (84.1%) and supporting the immune system (72.5%). However, less than half of participants believed in their beneficial effects on overweight/obesity (42.3%), stress management (35%), mental health/stress (29.2%), and heart health (28.7%).</p><p><strong>Conclusions: </strong>The obtained findings indicate sufficient levels of knowledge about prebiotics and probiotics among a population sample of Saudi adults. However, enhanced educational efforts and optimized strategies for promoting a comprehensive awareness and understanding of probiotics and prebiotics are recommended.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602206","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}
引用次数: 0
Circulating mucosal-like IgA responses increase with severity of Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome. 循环粘膜样 IgA 反应随普马拉正传病毒引起的出血热伴肾综合征的严重程度而增加。
IF 5.7 2区 医学
Frontiers in Immunology Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI: 10.3389/fimmu.2024.1480041
Luz E Cabrera, Cienna Buckner, Veronica Then, Sanna Mäki, Olli Vapalahti, Antti Vaheri, Jussi Hepojoki, Johanna Tietäväinen, Satu Mäkelä, Jukka Mustonen, Tomas Strandin
{"title":"Circulating mucosal-like IgA responses increase with severity of Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome.","authors":"Luz E Cabrera, Cienna Buckner, Veronica Then, Sanna Mäki, Olli Vapalahti, Antti Vaheri, Jussi Hepojoki, Johanna Tietäväinen, Satu Mäkelä, Jukka Mustonen, Tomas Strandin","doi":"10.3389/fimmu.2024.1480041","DOIUrl":"https://doi.org/10.3389/fimmu.2024.1480041","url":null,"abstract":"<p><p>Old World Orthohantaviruses cause hemorrhagic fever with renal syndrome (HFRS) characterized by increased vascular permeability and acute kidney injury (AKI). Despite the systemic nature of the disease, the virus enters humans through inhalation and therefore initially encounters the immunoglobulin class A (IgA) dominated mucosal immune system. Herein, we characterized systemic IgA responses and their potential relationship to the mucosal immune activation by examining blood samples obtained from patients hospitalized due to acute Puumala orthohantavirus infection. Our findings reveal increased frequencies of putative IgA-expressing circulating mucosal-associated B1 cells and plasmablasts, as well as elevated levels of polyreactive, polymeric, virus-specific and secretory IgA in the acute stage of the disease. Importantly, the levels of circulating virus-specific and secretory IgA, as well as the putative IgA+ B1 cells, increased with the severity of AKI. Furthermore, circulating polymeric IgA displayed enhanced effector functions by forming stable complexes with the IgA receptor CD89 and induced pro-inflammatory neutrophil responses. These results suggest that excessive levels of circulating mucosal-like IgA might serve as a biomarker for HFRS disease progression.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602229","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}
引用次数: 0
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