ImmunoTargets and Therapy最新文献

{"title":"Unveiling a ceRNA Network Involving IL-8 and TNF-α in Active Generalized Vitiligo by Multi-Omics Integration.","authors":"Kang Ge, Yilu Zhao, Ruzhi Zhang","doi":"10.2147/ITT.S595534","DOIUrl":"10.2147/ITT.S595534","url":null,"abstract":"<p><strong>Background: </strong>Active generalised vitiligo (AGV) is an autoimmune disorder characterised by progressive melanocyte loss. However, the molecular mechanisms underlying AGV, particularly the roles of non-coding RNAs and their interaction with proteomic changes, remain poorly understood. The aim of this study was to systematically identify key regulatory networks and molecular changes in AGV by integrating proteomic and whole-transcriptome data.</p><p><strong>Methods: </strong>Data-independent acquisition mass spectrometry (DIA-MS) and whole transcriptome sequencing (WTS) were performed on whole blood samples from three AGV patients and three healthy individuals (HIs). Bioinformatic analyses were then used to identify differentially expressed proteins (DEPs), messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs). Co-expression and competing endogenous RNA (ceRNA) networks were constructed and visualised using Cytoscape. Key hub genes and cytokine levels were then validated using quantitative reverse transcription PCR (qRT-PCR) and immunoassays in an independent cohort.</p><p><strong>Results: </strong>We identified 15 DEPs and 669 differentially expressed mRNAs (DEmRNAs), as well as significant alterations in 258 lncRNAs, 29 miRNAs and 44 circRNAs in AGV. Functional enrichment analysis revealed their involvement in chemokine signaling and lysosomal pathways. Protein-protein interaction network analysis revealed ten hub genes, including CXCL8, CXCR1, CXCR2 and IL1R2. We established a core ceRNA regulatory network featuring long non-coding RNAs (eg NUTM2B-AS1, LINC00894), circular RNAs (eg ASAP1, CDR2) and microRNAs (eg hsa-mir-3613-3p, hsa-mir-511-5p) that potentially modulate inflammatory responses. Experimental validation confirmed significantly elevated levels of the pro-inflammatory cytokines IL-8 and TNF-α in AGV patients, and qRT-PCR results for nine of the ten hub genes were consistent with the sequencing data.</p><p><strong>Conclusion: </strong>Our integrated multi-omics analysis uncovers a novel ceRNA network and highlights the significant upregulation of IL-8 and TNF-α in AGV. These findings provide new insights into the post-transcriptional regulatory mechanisms and inflammatory pathways driving AGV and offer potential therapeutic targets.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"595534"},"PeriodicalIF":4.1,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13250246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148228526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrin alpha8beta1 is Identified as a Potential CAR-T Target for BCMA-Resistant Relapsed Multiple Myeloma.","authors":"Suiping Liu, Jieying Wu, Jiayu Liu, Kangxiu Wu, Yanyan Huang, Suxia Geng, Yulian Wang, Jianyu Weng, Xin Du, Peilong Lai","doi":"10.2147/ITT.S605729","DOIUrl":"10.2147/ITT.S605729","url":null,"abstract":"<p><strong>Background: </strong>B cell maturation antigen (BCMA)-targeted chimeric antigen receptor T cell (CAR-T) therapy has improved outcomes for relapsed/refractory multiple myeloma (R/R MM), but most patients eventually relapse, largely due to antigen escape, clonal heterogeneity, and immune-evasive tumor subclones. Novel targets are urgently needed to complement BCMA CAR-T and reduce relapse.</p><p><strong>Methods: </strong>We analyzed several single-cell transcriptomic datasets from patients who relapsed after BCMA CAR-T to identify relapse-associated surface antigens. We characterized ITGA8 expression in normal tissues and hematopoietic cells, evaluated its biological function in myeloma cells, and generated α8β1-targeted CAR-T cells. Preclinical efficacy was assessed in vitro and in xenograft models in combination with BCMA CAR-T.</p><p><strong>Results: </strong>ITGA8 was significantly enriched in MM cells at early relapse following BCMA CAR-T therapy, marking a quiescent, immune-evasive subpopulation. ITGA8 was absent from normal hematopoietic stem and immune cells but showed restricted expression in vascular smooth muscle cells. α8β1 CAR-T specifically lysed ITGA8-positive myeloma cells and complemented with BCMA CAR-T to control tumor in models mimicking antigen loss.</p><p><strong>Conclusion: </strong>This preclinical proof-of-concept study identifies integrin α8β1 as a potential CAR-T target worthy of further development for BCMA-resistant relapsed MM. While short-term tumor control was improved, this does not equate to validated clinical relapse prevention. Safety related to off-tumor expression in non-hematopoietic tissues remains to be fully evaluated.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"605729"},"PeriodicalIF":4.1,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13225147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148151681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Review of Immunotherapy in Colorectal Cancer: From Mechanisms to Nursing Interventions.","authors":"Qiuyu Zhu, Yongwei Lai, Jie Zhao, Zhihong Zhang, Xiaoli Cui, Mengyuan Kou","doi":"10.2147/ITT.S603959","DOIUrl":"10.2147/ITT.S603959","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a highly prevalent malignant tumor of the digestive tract worldwide, with significant regional variations in its epidemiological characteristics. Traditional treatments including surgery, chemotherapy, and radiotherapy have limited efficacy and substantial adverse events, which can no longer meet clinical needs. In recent years, immunotherapy has brought new breakthroughs for CRC by reshaping the tumor microenvironment (TME) and blocking tumor immune escape. This review systematically summarizes the core mechanisms and clinical applications of major immunotherapies such as immune checkpoint inhibitors (ICIs) and oncolytic viruses (OVs). We focus on individualized treatment selection for different molecular subtypes (pMMR/MSS vs. dMMR/MSI-H), biomarker screening, efficacy evaluation, drug resistance mechanisms, and countermeasures. We also discuss novel targets and biomarker optimization for precision therapy. In addition, given the unique immune-related adverse events, we introduce the CRC \"SSEIE\" nursing model and its value in whole-process management. This review integrates the latest advances in CRC immunotherapy and nursing interventions, providing a reference for optimizing clinical regimens, improving nursing quality, and enhancing patient prognosis.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"603959"},"PeriodicalIF":4.1,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13222602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148144815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Immune Architecture of Eosinophilic Esophagitis: Mechanisms, Therapeutic Targets, and Precision Management.","authors":"Luisa Bertin, Federico Caldart, Alberto Barchi, Niccolò Seregni, Andrea Pasta, Francesco Calabrese, Elisa Marabotto, Amir Mari, Amir Farah, Emma Sirinic, Andrea Sorge, Matteo Ghisa, Javier Chahuán, Vincenzo Savarino, Edoardo Vincenzo Savarino","doi":"10.2147/ITT.S510865","DOIUrl":"10.2147/ITT.S510865","url":null,"abstract":"<p><strong>Background: </strong>Eosinophilic esophagitis (EoE) is a chronic, allergen-driven, type 2 immune-mediated disease of the esophagus defined by symptoms of esophageal dysfunction and eosinophil-predominant mucosal inflammation (≥15 eosinophils per high-power field), with a rising global prevalence now exceeding 1 in 1,000 individuals in Western countries. Its pathogenesis extends far beyond eosinophils, encompassing epithelial alarmin signaling (TSLP, IL-33, IL-18), ILC2 and Th2 immune activation, and a convergent effector network of eosinophils, mast cells, and fibroblasts that drives barrier disruption and progressive fibrostenotic remodeling.</p><p><strong>Purpose: </strong>This narrative review synthesizes current evidence on the multi-layered immunopathogenesis of EoE, the evolving conceptualization of disease remission, established and emerging therapeutic options, and precision medicine strategies incorporating phenotypic and molecular endotype classification.</p><p><strong>Key findings: </strong>EoE shares a pathophysiologic continuum with other atopic diseases, underpinned by convergent type 2 immune mechanisms and epithelial barrier gene defects. A recently characterized ILC2-amphiregulin-EGFR axis directly drives structural esophageal remodeling independent of eosinophil recruitment, providing a mechanistic explanation for the histology-symptom dissociation that limits several biologic therapies. First-line therapies-proton pump inhibitors (PPIs), swallowed topical corticosteroids (STCs), and dietary elimination-achieve histologic remission in 45-90% of patients. Dupilumab, the first approved biologic, achieves histologic remission in approximately 59-60% of patients versus 5-6% with placebo at week 24. An expanding pipeline targets IL-13, IL-5R, TSLP, mast cells, and JAK-STAT pathways alongside optimized steroid formulations and oral small molecules.</p><p><strong>Conclusion: </strong>EoE is entering an era of precision therapeutics. Integrating molecular endotyping, multi-effector immunopathology, and multidimensional disease activity assessment will be essential to optimize long-term outcomes, prevent fibrostenotic progression, and individualize the expanding armamentarium of targeted therapies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"510865"},"PeriodicalIF":4.1,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13227543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148158406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in the Management of Mediator-Related Symptoms in Non-Advanced Systemic Mastocytosis.","authors":"Theo Gülen, Vito Sabato","doi":"10.2147/ITT.S609692","DOIUrl":"10.2147/ITT.S609692","url":null,"abstract":"<p><p>Systemic mastocytosis (SM) is a rarely occurring clonal mast-cell disorder defined by aberrant mast-cell accumulation and episodic or chronic mediator release, giving rise to a broad range of manifestations from pruritus and flushing to gastrointestinal symptoms and anaphylaxis. In non-advanced SM, mediator-related symptoms are the major source of morbidity and substantially impair quality of life. Traditional symptom-directed therapies-including antihistamines, leukotriene modifiers, and mast-cell stabilizers-remain the foundation of care, but a subset of patients experience persistent, refractory symptoms. Advances in mast-cell biology have expanded therapeutic options for these patients, including selective KIT inhibitors, mast-cell--modulating small molecules, inhibitory-receptor agonists, epithelial-derived cytokine blockade, and agents targeting IgE-dependent and IgE-independent activation pathways. Key gaps remain, including the absence of validated biomarkers that distinguish activation from mast-cell burden, limited long-term safety data, and uncertainty around optimal dosing strategies. This review summarizes current understanding of mediator-driven disease in non-advanced SM and highlights targeted, mechanism-based therapies for refractory symptoms.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"609692"},"PeriodicalIF":4.1,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13221442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Prognostic Clinical Features in Grade 4 Immune-Related Adverse Events: A Triangulation Study.","authors":"Yulin Wu, Junyao Chen, Sijia Tian, Zhaojie Lin, Yong Li, Cuihan Wang, Qianying Lu, Lu Lu, Yanmei Zhao","doi":"10.2147/ITT.S609130","DOIUrl":"10.2147/ITT.S609130","url":null,"abstract":"<p><strong>Background: </strong>Grade 4 immune-related adverse events (irAEs) is life-threatening complications of immune checkpoint inhibitor therapy. Due to its rarity and scarcity of data, there is a lack of systematic research on key factors influencing poor prognosis. This exploratory study aimed to identify clinical features robustly associated with mortality in patients with grade 4 irAEs. Given the extremely small sample size and high‑dimensional data, a triangulation approach integrating traditional univariate statistics and machine learning to maximize the reliability of feature selection.</p><p><strong>Methods: </strong>This study included 26 cancer patients admitted to the ICU for grade 4 irAEs. To maximize robustness from limited data, a \"triangulation\" approach was employed. Prognostic features were independently identified through two parallel approaches: (1) traditional univariate statistical analysis, and (2) multiple machine learning algorithms evaluated by Leave-One-out Cross-Validation. Features consistently highlighted as significant by both independent methodologies were integrated to form a final high-confidence feature set.</p><p><strong>Results: </strong>Univariate analysis identified 21 features significantly associated with mortality. Machine learning analysis refined this to 11 important features. Through \"triangulation\", 8 features were consistently validated: body mass index and VEGF-inhibitors were inversely associated with mortality, while vasopressor therapy, oxygen therapy, lactate levels at day 1 and 2, pneumonia and percentage of neutrophils, exhibited a positive correlation with the mortality.</p><p><strong>Conclusion: </strong>This small-sample exploratory study identified 8 routinely available early ICU clinical features robustly associated with mortality in grade 4 irAEs patients using a \"triangulation\" framework. These characteristics highlight the pivotal roles of shock, respiratory failure, and inflammation. While not directly constructing a clinical prediction model, they may facilitate early risk stratification and provide hypotheses for prioritized validation in future large-sample studies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"609130"},"PeriodicalIF":4.1,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13222628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148144850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Exploratory in vitro Study of Cytotoxicity and Cytokine Profiling of Cytokine-Induced Killer (CIK) Cells Against HCT-15 Colorectal Cancer (CRC) Cells.","authors":"Sze-Piaw Chin, Natasha Najwa Nor Arfuzir, Vivian Wai-Ping Kong, Soon-Keng Cheong","doi":"10.2147/ITT.S594441","DOIUrl":"10.2147/ITT.S594441","url":null,"abstract":"<p><strong>Background: </strong>Cytokine-induced killer (CIK) cells are a promising adoptive immunotherapy due to their non-major histocompatibility complex (MHC)-restricted cytotoxicity. However, their cytokine-mediated response against CRC remains poorly defined.</p><p><strong>Methods: </strong>In this exploratory study, CIK cells were generated from three healthy donors and one metastatic CRC patient. Phenotypes were assessed by flow cytometry. Cytotoxicity against the HCT-15 CRC cell line was evaluated at multiple effector-to-target (E:T) ratios (1:5 to 40:1). Combination treatment with 5-fluorouracil (5-FU) and cytokine profiling using a 105-plex array were performed using CIK cells from donor 2 and donor 3, respectively.</p><p><strong>Results: </strong>CIK cells derived from one CRC patient exhibited phenotypic characteristics (CD3⁺CD8⁺ 85.91%, CD3⁺CD56⁺ 27.81%) comparable to the range observed in three healthy donors. Co-culture with CIK cells from donor 1 resulted in reduced HCT-15 viability at higher E:T ratios, with viability decreasing to 8.98 ± 0.61% and 8.08 ± 2.00% at 20:1 and 40:1, respectively. In combination experiments, HCT-15 viability was reduced to 1.02 ± 1.01% at an E:T ratio of 20:1 when co-cultured with CIK from donor 2 and treated with 5-FU. Similar reductions were observed with CIK cells from donor 3 and the CRC patient, reaching 2.60 ± 5.86% and 0.0% at 20:1, and 0.0% at 40:1 ratio for both donors. CIK cells from all donors showed dose-dependent reduction in cell viability against HCT-15 cells. Cytokine profiling of CIK from donor 3 identified changes in immune-related factors, including upregulation of interferon gamma-inducible chemokines (CXCL9 and CXCL10), alongside downregulation of immunosuppressive mediators such as TIM-3 and VEGF.</p><p><strong>Conclusion: </strong>This exploratory study demonstrates that functional CIK cells can be generated from healthy individuals and CRC patients, with observed cytotoxic activity against HCT-15 cells. The findings suggest potential immunomodulatory effects and support further investigation of CIK cells in combination strategies; however, larger patient cohorts and functional validation studies are required.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"594441"},"PeriodicalIF":4.1,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13209146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148044055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an Active Chimeric IL13Rα2 ADC for Diffuse Intrinsic Pontine Glioma.","authors":"Xiaolei Lian, Victoria J Allanson, Samuel V Rasmussen, Shefali Chauhan, Guak-Kim Tan, Paige Morrow, Kyle Hanson, Emily Bing Lian, Anthony R Haight, Tyuji Hoshino, Xianzhi Liu, Noah E Berlow, Charles Keller, Yajun Lian","doi":"10.2147/ITT.S575767","DOIUrl":"10.2147/ITT.S575767","url":null,"abstract":"<p><strong>Introduction: </strong>Diffuse intrinsic pontine glioma (DIPG) is a rare pediatric brain tumor with a critical unmet need due to the lack of approved, curative interventions available. The interweaving of malignant cells with normal tissue makes surgical extraction essentially impossible, and radiation provides only transient benefit. The recent ONC201 FDA approval, however, suggests DIPG therapy is tractable. Having identified overexpression of IL13Rα2 in DIPG tumor tissue versus normal brain tissue, we investigated binding of commercially available IL13Rα2 monoclonal antibodies. The top candidate antibody was used to generate a chimeric antibody, to which we conjugated deruxtecan to create a preclinical therapeutic candidate.</p><p><strong>Methods: </strong>We validated the novel antibody-drug conjugate (ADC) in vitro, demonstrating dose-dependent, IL13Rα2 expression-dependent cell death. We further validated the novel ADC ex ovo in quail xenograft models of DIPG and in vivo in a mouse xenograft model.</p><p><strong>Results: </strong>The ADC showed tumor reduction in the ex ovo quail embryo model for both IL13Rα2-high and IL13Rα2-low DIPG cell models. A proof-of-concept in vivo mouse xenograft experiment demonstrated a reduction in tumor volume beyond antibody treatment alone.</p><p><strong>Discussion: </strong>The work here represents an important milestone in preclinical development of a novel deruxtecan-based ADC agent for an intractable pediatric brain cancer, concurrent with other ADC agents demonstrating real-world clinical efficacy and gaining approvals in multiple disease indications.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"575767"},"PeriodicalIF":4.1,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13199871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148035655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Review of Aryl Hydrocarbon Receptor-Mediated Immune Regulation in Cutaneous Squamous Cell Carcinoma Progression.","authors":"Huiyan Han, Qinyi Dong, Zijian Zhang, Siying Li, Han Zhang, Xinman Wang, Jiahao Bai, Lei Shi, Xiaoyi Fu, Kaili Zheng, Lili Liang","doi":"10.2147/ITT.S601152","DOIUrl":"10.2147/ITT.S601152","url":null,"abstract":"<p><p>The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that was initially discovered for its role in mediating the toxicity of environmental pollutants such as dioxins. Recent studies have demonstrated that AhR plays significant roles in various physiological and pathological processes, including immune regulation and tumor development. Cutaneous squamous cell carcinoma (cSCC), the second most common skin malignancy, is closely associated with the immune microenvironment. This review systematically outlines the structure, function, and signaling pathways of AhR, as well as its role in the immune system, with a focus on how AhR influences the progression of cSCC by regulating the functions of various immune cells, including T cells, dendritic cells, macrophages, and myeloid-derived suppressor cells. In particular, this review highlights the central role of the \"tryptophan-kynurenine-AhR\" axis, along with AhR-mediated regulation of immune checkpoints (such as PD-1/PD-L1, CTLA-4, and TIM-3), its crosstalk with inflammatory signaling pathways (including NF-κB, STAT3, and TGF-β), and the impact of AhR on antigen presentation and immunoediting. Furthermore, it discusses the role of AhR ligands in cSCC and the potential of targeting AhR for therapy, providing a novel theoretical foundation and strategic insights for the immunotherapy of cSCC. This review systematically summarizes the immunomodulatory mechanisms of AhR, integrating findings from studies specific to cSCC and those from other tumor types. It should be noted that some mechanistic evidence is derived from non-cSCC research models, and its applicability to cSCC requires further validation.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"601152"},"PeriodicalIF":4.1,"publicationDate":"2026-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13189078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147989320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carcinoembryonic Antigen Flare Under Oxaliplatin-Based Chemotherapy Predicts Benefit from Nivolumab in Metastatic Microsatellite-Stable Colorectal Cancer - A Post Hoc Analysis of METIMMOX Trial Data.","authors":"Sebastian Meltzer, Silje Sjåvik Landmark, Jūratė Šaltytė Benth, Anne Negård, Hanne Mari Hamre, Christian Kersten, Eva Hofsli, Marianne Grønlie Guren, Halfdan Sorbye, Kjersti Flatmark, Anne Hansen Ree","doi":"10.2147/ITT.S594176","DOIUrl":"10.2147/ITT.S594176","url":null,"abstract":"<p><strong>Background: </strong>The randomized METIMMOX trial evaluated short-course oxaliplatin-based chemotherapy alternating with the immune checkpoint inhibitor nivolumab in patients with previously untreated, unresectable abdominal metastases from microsatellite-stable/mismatch repair-proficient colorectal cancer. A subgroup receiving this experimental treatment showed remarkably improved outcome compared to control arm patients who received chemotherapy alone and had median progression-free survival (PFS) of 9.3 months. We examined whether the kinetics of serum carcinoembryonic antigen (CEA) could provide insights into responsiveness to the METIMMOX regimen.</p><p><strong>Methods: </strong>Patients were randomly assigned to the control arm (oxaliplatin with bolus 5-fluorouracil/folinic acid, Q2W) or the experimental arm (alternating two cycles of chemotherapy Q2W and nivolumab Q2W). In this post hoc biomarker analysis, CEA levels were measured at baseline, at each treatment administration, and every two months during prespecified treatment breaks. Patients were categorized according to CEA kinetics-Flare (transient ≥20% increase above baseline), Non-responding (gradual increase), and Stable/Responding (values around baseline or gradually decreasing).</p><p><strong>Results: </strong>Flare comprised 16 out of 71 patients. According to Log rank test, experimental-arm Flare (n = 6) had significantly improved PFS (median 34.9 months) compared to Stable/Responding (n = 21; median PFS 9.9 months; <i>p</i> = 0.005) and Non-responding (n = 9; median PFS 2.1 months; <i>p</i> = 0.007). Flare was not associated with improved PFS for control-arm subjects. Adjusted Cox regression analysis indicated that experimental-arm Flare exhibited a lower progression risk than Non-responding for up to 6.2 months, creating an observation period for a potential decrease following the initial increase.</p><p><strong>Conclusion: </strong>CEA-Flare may indicate immune checkpoint inhibitor responsiveness following short-course oxaliplatin-based chemotherapy in this patient population; however, this is an exploratory finding that requires prospective validation.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"594176"},"PeriodicalIF":4.1,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13182746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147975904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}