Frontiers in Immunology最新文献

{"title":"PD-1 inhibitor combined with TPF induction chemotherapy in locally advanced nasopharyngeal carcinoma: a retrospective study of efficacy and safety.","authors":"Weiwei Zhang, Yousheng Meng, Ping Zhang, Dujuan Tian, Xianghua Zeng, Mingqing Dong, Lang He","doi":"10.3389/fimmu.2025.1654616","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1654616","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of PD-1 inhibitors in the induction therapy of locally advanced nasopharyngeal carcinoma (LA-NPC) remains unclear. The aim of this study was to retrospectively investigate the efficacy and safety of PD-1 inhibitor combined with induction chemotherapy in patients with LA-NPC.</p><p><strong>Patients and methods: </strong>A retrospective study was conducted on 158 LA-NPC patients, 80 patients received TPF (nab-paclitaxel, cisplatin and 5-fuorouracil) induction chemotherapy, and 78 patients received TPF-ICB (TPF plus PD-1 inhibitor) chemoimmunotherapy. Treatment response was evaluated immediately following completion of induction therapy using RECIST v1.1 criteria, including cervical lymph nodes and primary nasopharynx lesions. Responses were categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD), with objective response rate (ORR) calculated as the combined CR+PR rate. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity assessment. Acute treatment-related toxicities during induction therapy were graded according to CTCAE v5.0 criteria and compared between treatment groups.</p><p><strong>Results: </strong>After induction therapy, the ORR in the TPF group was significantly lower than that in the TPF-ICB group (71.2% vs. 88.5%, <i>p</i> = 0.007). The complete response (CR) rate in the TPF-ICB group was significantly higher than in the TPF group (29.5% vs. 11.3%, <i>p</i> = 0.004). The 3 and 5 years PFS rates in TPF-ICB group were 99% and 95%, which were significantly higher than the TPF group (89% and 87%, both <i>p</i> < 0.05). The 3-year (99% vs. 89%, <i>p</i> <0.001) and 5-years OS rates (95% vs. 87%, <i>p</i> < 0.0001) were superior in the TPF-ICB group. Grade ≥3 TRAEs occurred in 7 (8.6%) and 12 (15.5%) patients in the TPF and TPF-ICB groups, respectively (<i>p</i> = 0.596).</p><p><strong>Conclusions: </strong>The induction therapy of PD-1 inhibitor combined with TPF showed high CR and ORR rates in LA-NPC, and the safety was acceptable.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1654616"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206150","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":"Review of advanced research on swine <i>Actinobacillus pleuropneumoniae</i> vaccine development strategy.","authors":"Adehanom Baraki Tesfaye, Rui Han, Zhengyu Tao, Liuchao You, Jiayao Zhu, Pengcheng Gao, Lei Fu, Yuefeng Chu","doi":"10.3389/fimmu.2025.1645610","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1645610","url":null,"abstract":"<p><p><i>Actinobacillus pleuropneumoniae</i> (App) infection is a major respiratory disease that causes severe economic losses. It is highly infectious and exhibits multiple serotypes, which complicates prevention and control. This review discusses the new-generation vaccine development strategies and the role of virulence factors-such as App toxins, capsular polysaccharide (CPS), lipopolysaccharide (LPS), and outer membrane proteins (OMPs)-in vaccine design. Traditional vaccines offer limited cross-protection, whereas live attenuated vaccines, subunit vaccines, and toxin-based vaccines show promising improvements in efficacy and safety. Current and near-generation subunit and toxin vaccines mainly focus on conserved antigens, incorporating App toxins, OMPs ApfA, and GALT, which significantly enhance cross-protection and safety. Other approaches, including DNA vaccines and combined multivalent vaccines targeting highly prevalent App serotypes and integrating antigens from other pathogens, represent a modern strategy aimed at enhancing cross-serotype protection, minimizing side effects, and enabling differentiating infected from vaccinated animal (DIVA) capability.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1645610"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206202","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":"Immunoproteasome components LMP2, PSME1, and PSME2 as novel tissue biomarkers predicting response and survival in neoadjuvant chemoimmunotherapy for resectable NSCLC.","authors":"Ru Xie, Ke Zhai, Jinming Yu, Miaoqing Zhao","doi":"10.3389/fimmu.2025.1654573","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1654573","url":null,"abstract":"<p><strong>Background: </strong>While neoadjuvant chemoimmunotherapy (NACI) improves outcomes in resectable non-small cell lung cancer (NSCLC), a significant subset of patients exhibits innate resistance. Biomarkers predicting response are urgently needed. Given the central role of antigen processing in immunotherapy efficacy, we investigated key immunoproteasome components-LMP2 (PSMB9), PSME1, and PSME2-as potential tissue-based biomarkers for NACI response and survival.</p><p><strong>Methods: </strong>Potential biomarker genes were identified through systematic literature review of NSCLC immunotherapy transcriptomic datasets. Candidate genes underwent validation in public databases (GEO, TCGA) via differential expression and Kaplan-Meier survival analysis. Protein expression of LMP2, PSME1, and PSME2 was assessed by immunohistochemistry (IHC) in pre-treatment tumor biopsies from a retrospective cohort of 50 resectable NSCLC patients treated with NACI (platinum-based chemotherapy + anti-PD-1/PD-L1). Pathologic response was categorized as major pathologic response (MPR, ≤10% residual viable tumor) or incomplete pathologic response (IPR). Associations with MPR, overall survival (OS), and independent prognostic value were evaluated.</p><p><strong>Results: </strong>Bioinformatic analysis identified LMP2, PSME1, and PSME2 as immunoproteasome subunits linked to antigen presentation pathways. In the clinical cohort, low pre-treatment intratumoral expression of LMP2, PSME1, and PSME2 (by IHC) significantly predicted MPR (<i>P</i> < 0.05). Specifically, IPR patients exhibited higher median IHC scores for all three proteins compared to MPR patients. Kaplan-Meier analysis demonstrated that high pre-treatment LMP2 expression was associated with significantly improved OS (median OS: Not Reached vs. 40.0 months, <i>P <</i>0.0104). Post-NACI pathological stage (ypTNM III-IV) correlated with worse OS (<i>P</i> = 0.0027). Multivariate Cox analysis confirmed MPR status (HR = 8.709, <i>P</i> = 0.003), and high pre-treatment LMP2 (HR = 0.051, <i>P</i> = 0.007) as independent prognostic factors for OS.</p><p><strong>Conclusion: </strong>Low pre-treatment expression of immunoproteasome subunits LMP2, PSME1, and PSME2 predicts favorable pathologic response to NACI in resectable NSCLC. High baseline LMP2 expression, along with MPR achievement, independently associates with improved survival. These findings nominate LMP2/PSME1/PSME2 as novel, IHC-detectable biomarkers for stratifying NACI response and prognosis, highlighting the critical role of antigen processing machinery in modulating treatment efficacy. Validation in larger prospective cohorts is warranted.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1654573"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206252","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":"Leveraging the role of the microbiome in endometriosis: novel non-invasive and therapeutic approaches.","authors":"Eleni Andria Kalopedis, Amine Zorgani, Dmitry A Zinovkin, Muruj Barri, C David Wood, Md Zahidul I Pranjol","doi":"10.3389/fimmu.2025.1631522","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1631522","url":null,"abstract":"<p><p>Endometriosis (EMS) is an oestrogen-dependent condition characterised by ectopic endometrial-like tissue growth with a chronic and inflammatory nature leading to severe symptoms and reduced quality of life. Emerging evidence implicates gut microbiome dysbiosis in EMS pathogenesis, driving chronic inflammation, immune dysfunction, and altered bacterial taxa within patient gut microbiome. This review examines the intricate relationship between gut dysbiosis and EMS, with a focus on immunomodulatory mechanisms and the downstream consequences of the bacterial contamination theory. It evaluates recent findings regarding microbial imbalances and microbial diversity, pinpointing gaps in current research that mandate further understanding. For example, while microbial markers like <i>Lactobacillus</i> depletion and elevated <i>Escherichia coli</i> have been observed in patients, their diagnostic potential remains poorly defined. Additionally, it addresses the broader implications of EMS, including its physical, mental and healthcare burdens. Simultaneously, critiquing current drawbacks in diagnostic and therapeutic strategies such as their invasiveness and limited efficacy. The review further evaluates novel microbiome-based strategies namely <i>Lactobacillus</i>-based probiotics and faecal microbiota transplantation (FMT), assessing their potential in modulating immune responses and alleviating EMS symptoms while considering associated challenges. Lastly, it highlights the emerging role of metabolomics in identifying non-invasive and diagnostic biomarkers like short-chain fatty acids (SCFAs), implicated in the interplay between microbial metabolites and immune signalling pathways in EMS.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1631522"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206345","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":"Identification of <i>HLA-A</i>, <i>HLA-B</i>, and <i>HLA-C</i> triple homozygous and double homozygous donors: a path toward synthetic superdonor advanced therapeutic medicinal products.","authors":"Daniel Naumovas, Barbara Rojas-Araya, Catalina M Polanco, Victor Andrade, Rita Čekauskienė, Beatričė Valatkaitė-Rakštienė, Inga Laurinaitytė, Artūras Jakubauskas, Mindaugas Stoškus, Laimonas Griškevičius, Ivan Nalvarte, Jose Inzunza, Daiva Baltriukienė, Jonathan Arias","doi":"10.3389/fimmu.2025.1626787","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1626787","url":null,"abstract":"<p><p>Human-induced pluripotent stem cells with broad immune compatibility are highly desirable for regenerative medicine applications. Human leukocyte antigen (HLA) class I homozygous cell sources are ideal for immune compatibility modeling. Here, we profile <i>HLA-A</i>, <i>HLA-B</i>, and <i>HLA-C</i> alleles in 3,496 Lithuanian donors genotyped at three-field resolution. The five most frequent alleles constitute 74.6% of <i>HLA-A</i>, 43.2% of <i>HLA-B</i>, and 59.2% of <i>HLA-C</i>, with HLA-A*02:01:01, HLA-B*07:02:01, and HLA-C*07:02:01 being the most common. Lithuanian allele frequencies closely resemble those of European-American and British populations. We identified 153 double homozygotes and 51 triple homozygotes for <i>HLA-A</i>, <i>HLA-B</i>, and <i>HLA-C</i>. Compatibility modeling showed that triple homozygous profiles match 60.5% of Lithuanians, 13.4% of the British population, and 7.4% of European-Americans. CRISPR-Cas9 guide RNA design yielded 54 candidates predicted to disrupt <i>HLA-A</i> or <i>HLA-B</i> while preserving <i>HLA-C</i>, producing edited profiles matching over 97.9% of Lithuanians, 95.7% of European-Americans, and 95.5% of the British population. Finally, we established 15 fibroblast lines from triple homozygotes as a bioresource for the derivation of human-induced pluripotent stem cells and immune compatibility studies.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1626787"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206240","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":"FBXO2 promotes hepatocellular carcinoma progression and sorafenib resistance by targeting USP49 for proteasomal degradation.","authors":"Sirui Hang, Qingqing Wang, Jie Zhang, Yiwei Dong, Bile Hu, Peter Wang, Liu Xu","doi":"10.3389/fimmu.2025.1660034","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1660034","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatocellular carcinoma (HCC) is a highly prevalent and lethal malignancy with limited treatment efficacy due to tumor heterogeneity and the development of drug resistance. Identifying novel molecular mechanisms that drive HCC progression and therapeutic resistance is critical. F-box only protein 2 (FBXO2), an E3 ubiquitin ligase, has recently been implicated in tumorigenesis. However, its role in HCC remains unclear.</p><p><strong>Methods: </strong>We employed CCK-8, EdU, Transwell, and wound healing assays to evaluate the functional role of FBXO2 in HCC cells. Furthermore, Western blotting, immunoprecipitation, <i>in vivo</i> ubiquitination assays, and cycloheximide chase analysis were conducted to investigate the molecular mechanisms through which FBXO2 contributes to tumor progression in HCC.</p><p><strong>Results: </strong>FBXO2 is significantly upregulated in HCC tissues and correlates with poor patient prognosis. Functional assays demonstrated that FBXO2 promotes HCC cell proliferation, migration, and invasion <i>in vitro</i>, while its silencing exerts tumor-suppressive effects. Mechanistically, FBXO2 directly binds to and targets the USP49 for ubiquitin-mediated proteasomal degradation. This degradation decreases USP49 stability and function, thereby enhancing oncogenic potential. Importantly, silencing USP49 reversed the inhibitory effects of FBXO2 knockdown, confirming the FBXO2/USP49 axis as a functional regulator of HCC aggressiveness. Furthermore, FBXO2 depletion significantly enhanced the sensitivity of HCC cells and xenograft tumors to sorafenib treatment.</p><p><strong>Conclusion: </strong>Collectively, our findings establish FBXO2 as a critical modulator of HCC progression and therapeutic resistance via USP49 degradation, highlighting FBXO2 as a promising therapeutic target for overcoming sorafenib resistance in HCC.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1660034"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206264","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":"Bridging the gap: ferroptosis of immune cells in the tumor microenvironment.","authors":"Weijing Wang, Huiyao Li, Shuai Liang, Yani Hu, Junli Ding, Xi Wu, Dong Hua","doi":"10.3389/fimmu.2025.1648432","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1648432","url":null,"abstract":"<p><p>Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, is increasingly recognized as a pivotal immunomodulatory mechanism within the tumor microenvironment (TME). Beyond its well-established role in tumor cell elimination, emerging evidence reveals that immune cell subsets exhibit distinct susceptibility to ferroptosis, with profound consequences for antitumor immunity. This review systematically delineates the dual and cell-type-specific roles of ferroptosis across innate and adaptive immune populations: while ferroptosis-mediated depletion of immunosuppressive cells potentiates antitumor responses, immunostimulatory cells critically depend on ferroptosis defense pathways to sustain their survival and function-their dysfunction exacerbates immune evasion. We further decode the metabolic and signaling networks that govern immune cell ferroptosis and their dynamic interplay with immunotherapy and engineered nanomaterials. Finally, we critically addressed key challenges in clinical translation, including biomarker development, cell-specific delivery, and design of nanomaterials to minimize off-target effects. By elucidating the immune context-dependence of ferroptosis, this review provides a framework for developing precision therapies that harness ferroptosis-immune crosstalk to improve cancer therapy in the clinic.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1648432"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206297","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":"Post-translational governance of NF-κB in cancer immunity: mechanisms and therapeutic horizons.","authors":"Yue Hong, Ying Fu, Qian Long","doi":"10.3389/fimmu.2025.1627084","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1627084","url":null,"abstract":"<p><p>Nuclear factor-κB (NF-κB) is a central transcriptional orchestrator of inflammation, immune modulation, and tumor progression. Beyond canonical signal transduction, the immunological functions of NF-κB are intricately governed by a spectrum of post-translational modifications (PTMs)-including phosphorylation, acetylation, ubiquitination, and methylation-that fine-tune its activation, nuclear translocation, DNA binding, and transcriptional specificity. In this Review, we explore how these context-dependent PTMs dynamically shape NF-κB's role in cancer immunity: promoting macrophage polarization, controlling antigen presentation by dendritic cells, regulating T cell exhaustion, and sustaining immunosuppressive networks within the tumor microenvironment. We further delineate how PTM-mediated NF-κB signaling interfaces with immune checkpoint expression-particularly PD-L1 and IDO1-and fuels resistance to immunotherapies. Emerging pharmacological strategies targeting NF-κB-modifying enzymes or degradation via PROTACs hold promise to reprogram the immune landscape. By integrating mechanistic insight with translational potential, we position NF-κB's post-translational regulation as a fertile axis for next-generation immunotherapeutic innovation.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1627084"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206168","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":"²²⁵Actinium-armed antibody targeting CCR8⁺ regulatory T cells synergizes with immunotherapy to promote tumor rejection in syngeneic colorectal cancer models.","authors":"Connor Frank, Zhiwen Xiao, Kevin J H Allen, Rubin Jiao, Mackenzie E Malo, Ekaterina Dadachova","doi":"10.3389/fimmu.2025.1662216","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1662216","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) remains a formidable threat to health worldwide. Immunotherapy with immune checkpoint inhibitors results in only a minority of CRC patients experiencing long-term progression-free survival, at the expense of significant autoimmune toxicity. Development of new therapeutics to \"wake up\" the immune system to fight CRC is necessary. Here we investigated for the first time radioimmunotherapy (RIT) directed towards CCR8, a marker of tumor-infiltrating immunosuppressive T-regulatory cells (ti-Tregs) as a method to recover anti-tumor immunity followed by immunotherapy in CRC models.</p><p><strong>Methods: </strong>225Actinium (²²⁵Ac)-labeled anti-CCR8 antibody and anti-CTLA-4 immunotherapy were used to assess their potential synergistic effects in syngeneic murine CRC models CT26 and MC38. The safety of all treatments was assessed through complete blood counts and blood chemistry. ²²⁵Ac-anti-CCR8 RIT-treated tumors were analyzed immunohistochemically for FoxP3 and CCR8 expression while mechanistic studies of tumor-infiltrating lymphocytes were done by flow cytometry.</p><p><strong>Results: </strong>²²⁵Ac-anti-CCR8 RIT alone demonstrated effectiveness in CRC models but dramatic anti-tumor response was observed when it was combined with anti-CTLA-4 immunotherapy. Immunotherapy alone failed to control tumor growth. Tumor immunohistochemistry post ²²⁵Ac-anti-CCR8 RIT showed ablation of CCR8⁺ ti-Tregs while flow cytometry analysis revealed CCR8-specific increased influx of effector CD8⁺ T cells, M1 macrophages and NK cells in comparison with ²²⁵Ac-control antibody.</p><p><strong>Conclusions: </strong>These data demonstrate a synergistic effect of anti-aCCR8 RIT with immunotherapy through enhancement of adaptive and innate anti-tumor responses. Further investigation of anti-CCR8 RIT as a potential cancer-agnostic agent and its combinations with other immunotherapy agents such as anti-PD-1, LAG3 or TIGIT is warranted.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1662216"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206220","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":"An interpretable machine learning model using multimodal pretreatment features predicts pathological complete response to neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma.","authors":"Xueping Wang, Wencheng Tan, Hui Sheng, Wenjia Zhou, Hailin Zheng, Kewei Huang, Jinfei Lin, Songhe Guo, Minjie Mao","doi":"10.3389/fimmu.2025.1660897","DOIUrl":"https://doi.org/10.3389/fimmu.2025.1660897","url":null,"abstract":"<p><strong>Background: </strong>Although neoadjuvant immunochemotherapy (nICT) has revolutionized the management of locally advanced esophageal squamous cell carcinoma (ESCC), the inability to accurately predict pathological complete response (pCR) remains a major barrier to treatment personalization. We aimed to develop and validate an interpretable machine learning (ML) model using pretreatment multimodal features to predict pCR prior to nICT initiation.</p><p><strong>Methods: </strong>In this retrospective study, 114 ESCC patients receiving nICT were randomly allocated into training (n=81) and validation (n=33) cohorts (7:3 ratio). Predictors of pCR were identified from pretreatment clinical variables, endoscopic ultrasonography, and hematological biomarkers via least absolute shrinkage and selection operator (LASSO) regression. Eight machine learning algorithms were implemented to construct prediction models. Model performance was assessed by area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Shapley Additive Explanations (SHAP) provided feature importance and model interpretability.</p><p><strong>Results: </strong>Following feature selection, 17 variables were incorporated into model construction. The Random Forest (RF) model demonstrated perfect discrimination in the training cohort (AUC = 1.000, sensitivity = 1.000, specificity = 1.000, PPV = 1.000, NPV = 1.000), while maintaining robust predictive ability in the independent validation cohort (AUC = 0.913, sensitivity = 0.733, specificity = 0.889, PPV = 0.846, NPV = 0.800). Decision curve analysis (DCA) confirmed favorable clinical utility. SHAP analysis identified alcohol consumption, circumferential involvement ≥50%, elevated neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), and alanine aminotransferase (ALT) as the key contributors to pCR prediction.</p><p><strong>Conclusions: </strong>We established a clinically applicable, interpretable ML model that accurately predicts pCR to nICT in ESCC by integrating multimodal pretreatment data. This tool may optimize patient selection for nICT and advance precision therapy paradigms.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1660897"},"PeriodicalIF":5.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206272","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}