{"title":"The Microbiota-gut-brain axis in vascular cognitive impairment: unraveling the mysterious link and therapeutic prospects.","authors":"Tingting Liu, Ying Li, Xuejiao Xiong, Xinxing Lai, Xiangqing Xu","doi":"10.3389/fimmu.2025.1648800","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1648800","url":null,"abstract":"<p><strong>Background: </strong>Vascular cognitive impairment (VCI) exhibits particularly high prevalence in East Asian populations. However, its pathogenesis remains elusive due to its multifactorial and complex nature. Emerging evidence highlights the microbiota-gut-brain axis as a novel and promising paradigm for elucidating VCI mechanisms and developing therapeutic interventions. This systematic review aims to synthesize recent advances in this field, offering critical perspectives to guide future research on VCI through the lens of gut-brain interactions. Notably, given Traditional Chinese Medicine's (TCM) holistic and multi-target therapeutic advantages, we incorporate TCM studies to complement conventional approaches.</p><p><strong>Methods: </strong>We systematically searched PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang database for relevant studies from their inception to March 31, 2025, and conducted a comprehensive review.</p><p><strong>Results: </strong>A total of 22 relevant studies were included in the final review. Current research primarily focused on analyzing the altered gut microbiota in VCI patients, with findings indicating significant changes in both the structure and abundance of gut microbiota. <i>Enterobacteriaceae</i> exhibited potential as a diagnostic biomarker for post-stroke cognitive impairment (PSCI) (AUC=0.629), while distinct microbial signatures involving <i>Bifidobacterium</i>, <i>Lactobacillus gasseri</i>, and <i>Anaerostipes hadrus</i> may effectively differentiated PSCI patients from stroke survivors without cognitive deficits (AUC values of 0.785, 0.792, and 0.750, respectively). Furthermore, multiple interventional studies from both basic and clinical research systematically explored the microbiota-gut-brain axis as a promising therapeutic target for VCI. They evaluated the efficacy of diverse approaches-such as fecal microbiota transplantation, aerobic exercise, pharmacological interventions, and acupuncture-on key outcome including gut microbiota composition, cognitive function, hippocampal integrity, and inflammatory markers. Basic experimental studies revealed that <i>Prevotella histicola</i>, <i>Clostridium butyricum</i>, aerobic exercise, and TCM improved cognitive function, whereas trimethylamine N-oxide exacerbated cognitive impairment. The efficacy of TCM was further confirmed by clinical studies.</p><p><strong>Conclusion: </strong>Research is in its early stages, but the microbiota-gut-brain axis already offers promising prospects for a deeper understanding and discovery of potential new therapeutic targets for VCI.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/prospero, identifier CRD42024560293.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1648800"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344726","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 : 2025-10-07eCollection Date: 2025-01-01DOI: 10.3389/fimmu.2025.1690388
Chunhong Liao, Hua Su, Fengzhen Li, Chenglong Wang, Sufang Yang, Zujie Qin, Ning Li
{"title":"Anti-inflammatory mechanism of total flavonoids from <i>Polygala fallax</i> Hemsl. based on network pharmacology, molecular docking, and experimental validation.","authors":"Chunhong Liao, Hua Su, Fengzhen Li, Chenglong Wang, Sufang Yang, Zujie Qin, Ning Li","doi":"10.3389/fimmu.2025.1690388","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1690388","url":null,"abstract":"<p><strong>Objective: </strong>To explored the anti-inflammatory mechanisms of total flavonoids of <i>Polygala fallax</i> Hemsl. (PFHF) using network pharmacology, molecular docking, and cellular experiments.</p><p><strong>Methods: </strong>Key components, targets, and pathways of PFHF were identified via literature and network pharmacology, with molecular docking and dynamics simulations validating binding to therapeutic targets. RAW264.7 cells were treated with lipopolysaccharide (LPS) to establish inflammation, and groups included blank controls, LPS-induced models, prednisolone acetate, and low/high-dose PFHF. Cytokine levels (IL-6, TNF-α, IL-1β) were measured by ELISA, while immunofluorescence assessed protein expression post-PFHF treatment.</p><p><strong>Results: </strong>Six major active components were identified, alongside 44 active components, 1,178 inflammatory genes, and 18 target genes. Core targets included IL-6, TNF, IL1B, INS, and CASP3. Gene Ontology (GO) analysis linked these targets to protein localization, membrane rafts, and receptor activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways highlighted IL-17, TNF, and NOD-like receptor signaling. Molecular docking confirmed rutin's strong binding to IL-6, TNF, IL-1β, INS, and CASP3. HPLC quantified rutin at 0.09 mg/mL. PFHF inhibited RAW264.7 proliferation with IC50 values of 206.32 µg/mL (24h) and 102.39 µg/mL (48h). High-dose PFHF reduced IL-6, TNF-α, and IL-1β (P<0.05) versus the model group. Immunofluorescence revealed elevated INS (P<0.05) and reduced CASP3 (P<0.01), iNOS, and Cox-2 (P<0.0001) in treated cells.</p><p><strong>Conclusion: </strong>PFHF exerts anti-inflammatory effects via IL-17 and TNF pathways, targeting IL-6, TNF-α, INS, IL-1β, and CASP3, mediated by rutin and other components.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1690388"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12539403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344871","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 : 2025-10-07eCollection Date: 2025-01-01DOI: 10.3389/fimmu.2025.1675780
Ekta Mukhopadhyay, César López Camacho, Adrian V S Hill, Ahmed M Salman
{"title":"Subcutaneous administration of the malaria R21/Matrix M vaccine and immune complex formation with anti-circumsporozoite protein mAb 2A10 elicit protective efficacy in mice.","authors":"Ekta Mukhopadhyay, César López Camacho, Adrian V S Hill, Ahmed M Salman","doi":"10.3389/fimmu.2025.1675780","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1675780","url":null,"abstract":"<p><strong>Introduction: </strong>R21, the most efficacious malaria vaccine to date, has been recommended by the World Health Organization (WHO) for the prevention of malaria in children. The current vaccination schedule requires three intramuscular doses per year. Optimizing vaccine administration strategies, including exploring alternative routes of immunization and novel vaccine formulations, has the potential to reduce the number of required doses to achieve high efficacy. Immune complexes (ICs), formed by combining antigens with their cognate antibodies, have been successfully employed in licensed poultry vaccines for viral diseases and are showing promise in preclinical studies for human viral vaccines. Co-delivery of antigen with immune complexes has been reported to enhance antibody titers in preclinical models.</p><p><strong>Methods: </strong>Here, we present the first report of the immunogenicity and short- term high protective efficacy of R21/Matrix-M administered via the subcutaneous (SC) route, as well as in a modified formulation as an immune complex (IC) (R21: anti-NANP mAb 2A10) with only two immunizations. We also evaluated co-administration of R21 with pre-formed ICs.</p><p><strong>Results: </strong>R21/MM administered via the SC route is immunogenic and more efficacious (100% in BALB/c mice) than the IM route. R21:2A10 IC/MM is immunogenic and induces sterile protection in BALB/c mice. Co-administration of R21/MM with R21:2A10 IC is immunogenic but less protective than IC/MM alone in BALB/c mice.</p><p><strong>Conclusion: </strong>While IC-based vaccination strategies have primarily been explored for viral diseases, this study represents the first application of this approach to a parasitic disease. Our findings provide new insights into the potential of alternative vaccine delivery strategies and immune complex platforms for improving malaria vaccination outcomes.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1675780"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12538652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344887","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":"Functional and phenotypic characterization of peripheral blood mononuclear cells from tuberculosis patients in Southern Thailand.","authors":"Pyae Sone Oo, Jomkwan Ongarj, Ratchanon Sophonmanee, Narisa Mohthong, Sahasawat Suksan, Natapohn Saowaphong, Rachel Tanner, Nawamin Pinpathomrat","doi":"10.3389/fimmu.2025.1639808","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1639808","url":null,"abstract":"<p><strong>Introduction: </strong>Tuberculosis (TB) remains a global health challenge, with active TB disease (ATB) and latent TB infection (LTBI) representing distinct immunological states. Understanding immune responses in these groups is critical for developing effective interventions. The complex nature of immune responses to <i>Mycobacterium tuberculosis</i> (<i>M.tb</i>) within and between different stages of TB, host evasion mechanisms of the bacterium, variable protection conferred by the BCG vaccine in adults, and lack of validated immune correlates of protection are among the key challenges to the successful control of TB.</p><p><strong>Methods: </strong>In the present study, we conducted functional and phenotypic characterization of peripheral blood mononuclear cells (PBMCs) from a cohort in Southern Thailand. We compared immune responses in individuals with ATB, LTBI and healthy controls (HC) using flow cytometry (ATB n = 9, LTBI n = 11, HC n = 10) and the mycobacterial growth inhibition assay (MGIA) (ATB n = 13, LTBI n = 15, HC n = 15).</p><p><strong>Results: </strong>MGIA revealed significantly enhanced control of BCG growth in the ATB group compared to LTBI and HC groups. Furthermore, NK cell frequency and TNF-α levels were significantly elevated in ATB compared to LTBI and HC groups, and CD4+ T cell TNF-α responses correlated with mycobacterial growth control.</p><p><strong>Discussion: </strong>The findings from this study demonstrate differential immune responses across TB stages in this cohort, identify potential cellular markers for TB diagnosis and monitoring, and may guide vaccine strategies and host-directed therapies.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1639808"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344723","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 : 2025-10-07eCollection Date: 2025-01-01DOI: 10.3389/fimmu.2025.1629118
Gabirel Astarloa-Pando, Victor Sandá, Ainhoa Amarilla-Irusta, Ainara Lopez-Pardo, Itxaso San Juan, Ainhoa Iturbe-Larrondo, Raquel Pérez-Garay, Silvia Pérez-Fernández, Borja Santos-Zorrozúa, Bárbara Manzanares-Martín, Raquel Bernardo, Carmen González, Alasne Uranga, Mercedes Rey, Marta Alonso, Elena Amutio, Juan J Mateos-Mazón, Juan C García-Ruiz, Olatz Zenarruzabeitia, Laura Amo, Francisco Borrego
{"title":"Dynamics of NK cell subsets following autologous hematopoietic stem cell transplantation in adult oncologic patients.","authors":"Gabirel Astarloa-Pando, Victor Sandá, Ainhoa Amarilla-Irusta, Ainara Lopez-Pardo, Itxaso San Juan, Ainhoa Iturbe-Larrondo, Raquel Pérez-Garay, Silvia Pérez-Fernández, Borja Santos-Zorrozúa, Bárbara Manzanares-Martín, Raquel Bernardo, Carmen González, Alasne Uranga, Mercedes Rey, Marta Alonso, Elena Amutio, Juan J Mateos-Mazón, Juan C García-Ruiz, Olatz Zenarruzabeitia, Laura Amo, Francisco Borrego","doi":"10.3389/fimmu.2025.1629118","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1629118","url":null,"abstract":"<p><p>Early immune reconstitution following autologous hematopoietic stem cell transplantation (autoHSCT) is associated with improved outcome in various cancers. Natural killer (NK) cells are the first lymphocyte subset to recover post-autoHSCT and play a crucial role in antitumor immunity. In this study, we have performed an in-depth characterization of NK cells in adult patients with different hematological malignancies. Our results revealed that, immediately after autoHSCT, NK cells transiently acquired a decidual-like phenotype, displayed a more immature and activated state, and exhibited an upregulation of inhibitory receptors and a downregulation of activating receptors. This decidual-like and activated phenotype was characterized by increased expression of CD56, CD9, CD49a, CD151, CD38 and HLA-DR. Additionally, we assessed plasma cytokine levels and identified associations between cytokine concentrations and NK cell phenotypic changes. <i>In vitro</i> experiments suggested that these phenotype alterations could modulate NK cell function. Finally, in patients with non-Hodgkin lymphoma (NHL), we observed a correlation between NK cell maturation status and progression-free survival. Collectively, our findings provide valuable insights into NK cell dynamics during immune reconstitution following autoHSCT and may inform of strategies for improving patients' management.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1629118"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344729","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 : 2025-10-07eCollection Date: 2025-01-01DOI: 10.3389/fimmu.2025.1658396
Enrico Maggi, Nadine Landolina, Francesca Romana Mariotti, Enrico Munari, Nicola Tumino, Paola Vacca, Bruno Azzarone, Lorenzo Moretta
{"title":"The innate immune response in SARS-CoV2 infection: focus on toll-like receptor 4 in severe disease outcomes.","authors":"Enrico Maggi, Nadine Landolina, Francesca Romana Mariotti, Enrico Munari, Nicola Tumino, Paola Vacca, Bruno Azzarone, Lorenzo Moretta","doi":"10.3389/fimmu.2025.1658396","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1658396","url":null,"abstract":"<p><p>Innate immunity is the first line of defense against infections, including the detection and response to SARS-CoV-2. Cells of the innate system are usually activated within hours after pathogen exposure and do not generate conventional immunological memory. In this review, the current knowledge of the innate immune cells and of pattern-recognition receptors in sensing and responding to SARS-CoV-2 to mount a protective response has been shortly reviewed. Subsequently, the evasion strategies of the virus, as the inhibition of IFN-I/III production and autophagic response, counteracting the innate cell activity (including NK cells), have been briefly outlined. In the course of the infection, these strategies are also capable of rendering dysfunctional most innate cells, thus deeply interfering with the onset and maintenance of adaptive immunity. Possible mechanism(s) for the maintenance of dysfunctional innate immune response are also discussed. In this context, the importance of a rapid and robust activation of innate immunity through toll-like receptor (TLR) 4 as a key paradigm central to host defense against COVID-19 pathogenesis is also illustrated. We also discuss how the viral excess plus inflammatory signals upregulating TLR4 on innate cells may initiate a vicious loop which maintains and improves hyperinflammation, leading to the most critical outcomes. Targeting the TLR4 or its signaling pathway may be a promising therapeutic strategy, offering the dual benefits of viral suppression and decreasing inflammation.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1658396"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344712","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 : 2025-10-07eCollection Date: 2025-01-01DOI: 10.3389/fimmu.2025.1623150
Ke Meng, Jing Chen, Junzhe Chen, Shengjie Sun, Hui Li, Guanzhou Zhou, Fei Pan
{"title":"Risk factors for steroid-refractory in immune checkpoint inhibitor-induced colitis: a retrospective cohort study.","authors":"Ke Meng, Jing Chen, Junzhe Chen, Shengjie Sun, Hui Li, Guanzhou Zhou, Fei Pan","doi":"10.3389/fimmu.2025.1623150","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1623150","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) represent an effective treatment for various malignant tumors. However, the utilization of ICIs is frequently accompanied by immune-related adverse events (irAEs), among which immune checkpoint inhibitor (ICI)-induced colitis is a notable complication. Current clinical guidelines recommend corticosteroids as the first-line therapy for ICI-induced colitis. Nevertheless, subset of patients fails to respond adequately to corticosteroid therapy, resulting in steroid refractoriness. At present, studies investigating the risk factors for steroid-refractory remain limited.</p><p><strong>Patients and methods: </strong>A retrospective analysis was conducted on patients diagnosed with ICI-induced colitis after malignant tumor treatment with ICIs. Data collected included demographics, tumor and ICIs types, time to colitis onset, number of ICIs treatments, clinical manifestations (diarrhea, abdominal pain, bloody stool, fever), endoscopic findings (ulcerative lesions, extent of lesion distribution), laboratory results, grades of diarrhea and colitis, and corticosteroid treatment response. Patients were stratified into steroid-responsive and steroid-refractory groups. Multivariate logistic regression analysis was employed to identify risk factors related to steroid-refractory. Kaplan-Meier survival analysis and log-rank tests were conducted to compare survival time differences between the two groups.</p><p><strong>Results: </strong>A total of 57 patients were included, with 45 patients in the steroid-responsive group and 12 patients in the steroid-refractory group. Univariate analysis revealed differences between the two groups in the time to colitis onset (median days: 97 vs. 141, <i>P</i> = 0.037), presence of fever (4.4% vs. 25.0%, <i>P</i> = 0.045), presence of ulcerative lesions (26.9% vs. 34.6%, <i>P</i> = 0.036), grades of colitis (<i>P</i> = 0.011), and serum interleukin-6 (IL-6) level (24.1 ± 20.5 pg/mL vs. 81.7 ± 38.7 pg/mL, <i>P</i> < 0.001). Multivariate regression analysis indicated that serum IL-6 level was an independent risk factor for steroid-refractory. Kaplan-Meier survival analysis showed no significant difference in survival time between the two groups.</p><p><strong>Conclusions: </strong>For patients with ICI-induced colitis, serum IL-6 level at colitis onset could serve as an independent risk indicator for predicting the efficacy of corticosteroid therapy. Early consideration of selective immunosuppressive therapy (SIT) may be warranted with caution for patients with high serum IL-6 level.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1623150"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344859","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 : 2025-10-07eCollection Date: 2025-01-01DOI: 10.3389/fimmu.2025.1685592
Chenfei Zhou, Yan Sun, Tao Liu, David P J van Dijk, Wenqi Xi, Jinling Jiang, Liting Guo, Feng Qi, Xuekun Zhang, Mengfan Jia, Jun Ji, Zhenggang Zhu, Sander S Rensen, Steven W M Olde Damink, Jun Zhang
{"title":"Clinical and body composition parameters as predictors of response to chemotherapy plus PD-1 inhibitor in gastric cancer.","authors":"Chenfei Zhou, Yan Sun, Tao Liu, David P J van Dijk, Wenqi Xi, Jinling Jiang, Liting Guo, Feng Qi, Xuekun Zhang, Mengfan Jia, Jun Ji, Zhenggang Zhu, Sander S Rensen, Steven W M Olde Damink, Jun Zhang","doi":"10.3389/fimmu.2025.1685592","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1685592","url":null,"abstract":"<p><strong>Background: </strong>Predicting the treatment efficacy of programmed cell death protein 1 (PD-1) inhibitors is crucial for guiding optimal treatment plans and preventing unnecessary complications for cancer patients. We aimed to develop a prediction model using clinical and body composition parameters to identify gastric cancer (GC) patients who would respond to chemotherapy plus PD-1 antibody.</p><p><strong>Methods: </strong>Clinical data of GC patients treated with chemotherapy plus PD-1 antibody (immunotherapy cohort, n = 120) or chemotherapy alone (chemotherapy cohort, n = 82) following surgical resection were reviewed as the training set. Patients treated with chemotherapy plus PD-1 antibody at an external center were included as the validation set (n = 43). Tumor regression grade (TRG) was recorded and classified as TRG0/1 or TRG2/3 during analysis. Body composition parameters were assessed on computed tomography images at the third lumbar vertebral level using the SliceOmatic software. Univariate and multivariate analyses were performed to identify parameters associated with TRG0/1, and then a logistic regression model was developed to stratify patients into the good and poor response groups.</p><p><strong>Results: </strong>In the training set, clinical and body composition parameters between the immunotherapy cohort and chemotherapy cohort were similar. Skeletal muscle radiation attenuation (SMRA), neutrophil-to-lymphocyte ratio (NLR), and weight loss were associated with TRG0/1 in the immunotherapy cohort. Subcutaneous adipose tissue index (SATI) and metastasis were identified in the chemotherapy cohort. A logistic regression model was developed to stratify immunotherapy cohort patients into two response groups with an area under the receiver operating characteristic curve (AUC) value of 0.728. In the immunotherapy cohort, patients stratified as good responders showed a higher TRG0/1 rate (37/55, 67.3%) than poor response patients (18/65, 27.7%, <i>p</i> < 0.001) and had better overall survival (<i>p</i> = 0.001). In the external validation set, patients stratified using the clinical model as good responders also showed a higher TRG0/1 rate (14/18, 77.8%) than poor response patients (9/25, 36.0%, <i>p</i> = 0.012).</p><p><strong>Conclusion: </strong>The prediction model consisting of SMRA, NLR, and weight loss could help identify GC patients who respond well to chemotherapy plus PD-1 antibody.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1685592"},"PeriodicalIF":5.9,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344861","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 : 2025-10-06eCollection Date: 2025-01-01DOI: 10.3389/fimmu.2025.1677358
Zahra Jamila Ikra, Qiutong Huang, Huiyang Yu, Gabrielle T Belz, Craig N Jenne, Nicolas Jacquelot
{"title":"Unspoken words: decoding the dialog between type 2 innate lymphoid cells and T cells.","authors":"Zahra Jamila Ikra, Qiutong Huang, Huiyang Yu, Gabrielle T Belz, Craig N Jenne, Nicolas Jacquelot","doi":"10.3389/fimmu.2025.1677358","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1677358","url":null,"abstract":"<p><p>Type 2 innate lymphoid cells (ILC2s) are critical mediators of type 2 immunity that play non-redundant context-dependent modulatory functions. Primarily associated with responses against helminths and allergens via the activation of a potent epithelial-ILC2 axis, a growing body of evidence also suggests that a crosstalk between ILC2 and T cells is equally important in maintaining tissue homeostasis. In barrier tissues and secondary lymphoid organs, ILC2s co-localize with T cells, forming hubs where bi-directional signals are exchanged. Here, we describe the diversity of functional interactions between ILC2s and T cells, detailing known contact-dependent and -independent mechanisms, including a relatively new and still poorly defined antigen-presenting function during inflammation. Understanding these complex interactions is necessary to fully elucidate how this specific crosstalk helps maintain tissue homeostasis and regulate inflammatory responses. Identifying the spatial and temporal specificities of these interactions will certainly open new avenues for future targeting of this axis to improve immune-mediated host protection.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1677358"},"PeriodicalIF":5.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344705","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 : 2025-10-06eCollection Date: 2025-01-01DOI: 10.3389/fimmu.2025.1707327
Xiaopeng Chen, Zhiqi Yang, Minghao Li
{"title":"Correction: Molecular regulatory mechanisms and diagnostic potential of dendritic cell-derived exosomes in liver transplantation: from immune tolerance induction to translational challenges.","authors":"Xiaopeng Chen, Zhiqi Yang, Minghao Li","doi":"10.3389/fimmu.2025.1707327","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1707327","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fimmu.2025.1657956.].</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1707327"},"PeriodicalIF":5.9,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145344725","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}