ImmunoTargets and Therapy最新文献

{"title":"Prognostic Significance of Tumor-Cell VISTA Expression on Survival Outcomes in Nivolumab-Treated Pleural Mesothelioma: The HOT1901 Retrospective Multi-Institutional Study.","authors":"Hiroshi Yokouchi, Hiroshi Nishihara, Yoshiyuki Kenmotsu, Kosuke Tsuji, Takayuki Kishikawa, Hajime Kikuchi, Eisaku Miyauchi, Yutaro Nagano, Kenya Kanazawa, Jun Sugisaka, Takayuki Ohkuri, Satoshi Oizumi","doi":"10.2147/ITT.S585001","DOIUrl":"10.2147/ITT.S585001","url":null,"abstract":"<p><strong>Background: </strong>Nivolumab is used as a second-line treatment for pleural mesothelioma (PM); however, predictive or prognostic biomarkers remain unclear. We aimed to identify factors associated with survival in nivolumab-treated PM patients.</p><p><strong>Methods: </strong>This retrospective, multi-institutional cohort study included patients with PM who received nivolumab monotherapy as a second-line or later treatment at 18 hospitals in Japan. We evaluated associations of progression-free survival (PFS) and overall survival (OS) with baseline clinical variables, protein expression in tumor tissue specimens obtained before first-line therapy by immunohistochemical (IHC), and tumor mutational and copy-number profiles detected by next-generation sequencing (NGS).</p><p><strong>Results: </strong>Fifty-five patients were enrolled, with evaluable IHC in 42 and NGS in 33. V-domain immunoglobulin suppressor of T-cell activation (VISTA) expression was classified as high or low using a cutoff of 10% VISTA-positive tumor cells. High VISTA expression (n=35) was significantly associated with improved PFS and OS compared with low expression (n=7) (PFS: median, 5.1 vs 2.4 months, p = 0.001; OS: median, 12.8 vs 4.3 months, p = 0.007). Multivariate analysis confirmed high VISTA expression as an independent predictor of prolonged PFS and OS (PFS: hazard ratio [HR] 0.14, p < 0.001; OS: HR 0.38, p = 0.044).</p><p><strong>Conclusion: </strong>Low tumor-cell VISTA expression was associated with poorer outcomes following nivolumab treatment; however, independent validation in prospective studies with a comparator arm is required before VISTA expression can be used to guide treatment selection. These findings support further investigation of biomarkers for combination strategies such as nivolumab-ipilimumab or chemoimmunotherapy in PM.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"585001"},"PeriodicalIF":4.1,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814346","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":"Blinatumomab for Pediatric High-Risk B-Cell Precursor Acute Lymphoblastic Leukemia: Safety, MRD Response and Survival in a Single-Center Retrospective Cohort [Removal].","authors":"","doi":"10.2147/ITT.S645886","DOIUrl":"10.2147/ITT.S645886","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.2147/ITT.S603087.].</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"645886"},"PeriodicalIF":4.1,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148867024","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":"Prognostic and Predictive Value of Peripheral CD8/PD-1/TCF-1 Positive T Cells in Non-Small Cell Lung Carcinoma Patients.","authors":"Anastasia Xagara, Maria Goulielmaki, Evangelia Chantzara, Filippos Koinis, Sotiris P Fortis, Dora Hatzidaki, Konstantinos Ntostoglou, George Christodoulopoulos, Emmanouil Saloustros, Sophia N Karagiannis, Teresa Frisan, Constantin N Baxevanis, Vassilis Georgoulias, Ioannis S Pateras, Athanasios Kotsakis","doi":"10.2147/ITT.S594870","DOIUrl":"10.2147/ITT.S594870","url":null,"abstract":"<p><strong>Introduction: </strong>Novel predictive biomarkers are needed to optimize immunotherapy-based treatment response in non-small cell lung carcinoma (NSCLC). T cell modulatory features may limit the ability of T cells to mount effective anti-tumor responses and could predict immune fitness and responsiveness to therapy. We investigated the prognostic and predictive value of CD8+ T cells with an exhausted phenotype, specifically those co-expressing Programmed Death 1 (PD-1) and T cell factor 1 (TCF-1), in peripheral blood of NSCLC patients before any systemic treatment.</p><p><strong>Methods: </strong>Two patient cohorts were analyzed: a) 32 patients with early and locally advanced disease (stage I-IIIA; cohort A) who did not receive immunotherapy, and b) 47 patients with advanced disease (stage IIIB-IV) who received chemo-immunotherapy. Multicolor flow cytometry was used to assess CD8+ T cell subpopulations co-expressing PD-1 and TCF-1.</p><p><strong>Results: </strong>PD-1+TCF1+ progenitor (early) exhausted T cells were found at high frequencies in all NSCLC patients compared with healthy donors, regardless of tumor stage. In cohort A, patients with high levels of CD3+CD8+PD-1+TCF1+ T cells had significantly improved DFS (<i>p</i>= 0.038), while those with high CD3+CD8+PD-1+TCF1- T cells had significantly worse DFS (<i>p</i>= 0.028). In cohort B, high levels of CD3+CD8+PD-1+TCF1+ T cells were associated with shorter PFS (<i>p</i>= 0.027). No association with OS was observed in cohort A. Conversely, in cohort B, high CD3+CD8+PD-1+TCF1+ T cell levels correlated with shorter OS (<i>p</i>= 0.045), while high CD3+CD8+PD-1+TCF1- T cell levels correlated with longer OS (<i>p</i>= 0.010).</p><p><strong>Conclusion: </strong>Therefore, here we show that circulating PD-1⁺TCF1+ T cells correlated differentially with treatment outcome in early and late NSCLC stage patients.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"594870"},"PeriodicalIF":4.1,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13450603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698004","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":"Increased Expression of HLA-DR and CD69 on Peripheral CD4⁺ T Cells Predicts Better Clinical Outcomes in Cutaneous Melanoma.","authors":"Ana Tomás, José Maximino, Hugo Nunes, Rute Salvador, Rafael Luís, Cheila Brito, Diana P Saraiva, Emanuel Gouveia, Carolina Pereira, Filipe Gonçalves, Victor Farricha, Elisabete Lopez Carvalho, Cecília Moura, Maria José Passos, Sofia Cristóvão-Ferreira, Patrícia M Pereira, Maria Guadalupe Cabral, Marta Pojo","doi":"10.2147/ITT.S606640","DOIUrl":"10.2147/ITT.S606640","url":null,"abstract":"<p><strong>Background: </strong>Cutaneous melanoma (CM) is an aggressive skin cancer with rising incidence, representing a growing public health concern. Despite the remarkable success of immune-checkpoint inhibitors (ICIs) in the management of advanced disease, mortality remains high due to therapy resistance. Identifying reliable prognostic and predictive biomarkers is therefore essential to improve patient stratification, optimize treatment selection, and minimize unnecessary toxicity.</p><p><strong>Methods: </strong>We comprehensively profiled the circulating immune landscape of 54 treatment-naïve CM patients by integrating flow cytometry immunophenotyping with clinicopathological data, and performed tumor gene expression analysis in a subset of 26 patients.</p><p><strong>Results: </strong>Elevated HLA-DR and CD69 expression on circulating CD4⁺ T cells, together with reduced circulating CD8⁺ T cell frequency, emerged as candidate prognostic biomarkers associated with improved survival. Prognostic models combining these immune variables with clinical covariates accurately stratified patients by overall survival (89.5% sensitivity, 72.7% specificity; AUC = 0.872, <i>p</i> < 0.0001) and progression/recurrence risk (75% sensitivity and 71.4% specificity; AUC = 0.763, <i>p</i> = 0.001). In a subset of 43 patients subsequently treated with ICIs, elevated baseline HLA-DR and CD69 expression on circulating CD4⁺ T cells was also associated with therapeutic benefit. A predictive model integrating these markers with clinical covariates achieved good discriminatory performance (65.2% sensitivity, 88.9% specificity; AUC = 0.775, <i>p</i> = 0.0027). Tumor gene expression profiling supported the role of IFN-γ-related signatures, previously linked to ICI response, as complementary prognostic and predictive tools.</p><p><strong>Conclusion: </strong>These findings highlight systemic CD4⁺ T cell activation status as a potential, easily measurable biomarker in CM, laying the foundation for future strategies to refine patient stratification and guiding immunotherapy decisions.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"606640"},"PeriodicalIF":4.1,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148593662","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":"Near Infrared Photoimmunotherapy for Lung Cancer: Recent Development and Perspective.","authors":"Ryu Okada, Mizuki Yamada, Mitsuo Sato, Kazuhide Sato","doi":"10.2147/ITT.S608901","DOIUrl":"10.2147/ITT.S608901","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the leading cause of cancer mortality worldwide, and despite advances in surgery, chemotherapy, radiotherapy, and immunotherapy, challenges persist due to off-target toxicity and limited specificity. Photodynamic therapy (PDT), a minimally invasive treatment using photosensitizers and light to induce ROS-mediated cell death, has been explored for early-stage lung cancer; however, its clinical utility remains limited by poor tissue penetration, nonspecific photosensitizer uptake, and oxygen dependence.</p><p><strong>Discussion: </strong>Near-infrared photoimmunotherapy (NIR-PIT) is a highly specific cancer treatment that overcomes many limitations of conventional PDT. It employs antibody-photoabsorber conjugates, such as monoclonal antibodies linked to IRDye700DX, which bind selectively to cancer cell surface antigens and are activated by 690-nm NIR light. This illumination induces a unique, non-ROS-dependent cell death, \"photochemosis\", marked by immediate physical disruption of cancer cell membranes. Beyond direct cytotoxicity, NIR-PIT elicits robust immunogenic cell death, promotes systemic antitumor immunity, and permits repeated treatment cycles without compromising safety. The air-rich lung environment and deep penetration of NIR light make lung cancer an ideal NIR-PIT candidate. Advances in light-delivery devices-including endoscopic catheters, flexible LED systems, and endovascular therapy-based technologies-have greatly improved the feasibility of targeting deep pulmonary lesions for clinical implementation. Moreover, the modular design of NIR-PIT allows adaptation to diverse tumor targets, including EGFR and components of the tumor microenvironment, broadening its applicability.</p><p><strong>Conclusion: </strong>In this review, we provide a comprehensive overview of the mechanisms, advantages, and recent technological innovations of NIR-PIT, with a focus on its potential as a transformative therapeutic approach for lung cancer.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"608901"},"PeriodicalIF":4.1,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13387190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550578","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":"Targeting BLyS and APRIL with Telitacicept versus Conventional Immunotherapy in Generalized Myasthenia Gravis: A Comparative Study.","authors":"Yingying Yang, Nan Kang, Ying Zhu, Chi Ma, Ruixia Zhu","doi":"10.2147/ITT.S616114","DOIUrl":"10.2147/ITT.S616114","url":null,"abstract":"<p><strong>Background: </strong>Telitacicept is approved for acetylcholine receptor antibody-positive generalized myasthenia gravis (AChR-Ab+ gMG) in China. Although clinical trials have demonstrated its efficacy, real-world outcomes and safety require validation. This study compared telitacicept with conventional immunotherapy in a broader AChR-Ab+ GMG population, bridging the gap between RCT data and real-world practice.</p><p><strong>Methods: </strong>This retrospective real-world study (ChiCTR2500109279) included 215 patients with AChR-Ab+ gMG, with 43 receiving telitacicept and 172 undergoing conventional immunotherapy. Propensity score matching (1:1) yielded 35 patients per group. Treatment response was assessed by changes in Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis Activities of Daily Living (ADL) scores, time to minimal symptom expression (MSE), and prednisone use.</p><p><strong>Results: </strong>At week 4, the telitacicept group showed greater improvements than the control group in both QMG and ADL scores (QMG: 3.63±1.48 vs 0.37±2.76, p<0.001; ADL: 2.80±1.13 vs 0.46±2.44, p<0.001). These benefits were more pronounced at week 24 and sustained throughout follow-up (QMG: 10.30±4.19 vs 2.86±3.21, p<0.001; ADL: 8.06±3.37 vs 2.63±2.07, p<0.001). The telitacicept group also reached MSE earlier (median 5 months) and had more patients achieving MSE by week 24 (57.1% vs 11.4%, p<0.001), with lower cumulative prednisone doses over 24 weeks (2325 mg vs 6525 mg, p<0.001). A progressive decrease in IgM/IgG ratio was observed during treatment. Telitacicept was well-tolerated with no serious adverse events.</p><p><strong>Conclusion: </strong>This real-world study demonstrates that telitacicept effectively improves symptoms and maintains stability in AChR Ab+ gMG patients, with faster onset, reduced corticosteroid dependence, and favorable safety versus conventional immunotherapy.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"616114"},"PeriodicalIF":4.1,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148521110","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":"Anlotinib Combined with Programmed Death-1/Programmed Death-Ligand 1 Inhibitor 9 Hydrochloride Suppresses Colorectal Cancer Progression by Inducing Neovascularization and Reprogramming the Tumor Immune Microenvironment in MSS Murine Model.","authors":"Junpeng Ma, Mingkun Wang, Kunnan Wang, Juyi Wen, Xiaoya Liu, Xiangfei Zhao","doi":"10.2147/ITT.S597338","DOIUrl":"10.2147/ITT.S597338","url":null,"abstract":"<p><strong>Background: </strong>Anlotinib, a novel multi-target tyrosine kinase inhibitor, has demonstrated promising antitumor efficacy by inhibiting angiogenesis. However, the potential therapeutic benefits and underlying mechanisms of combining anlotinib with immune checkpoint inhibitors in colorectal cancer remain unclear.</p><p><strong>Methods: </strong>Syngeneic models of colorectal cancer were established and treated with anlotinib, PD-1/PD-L1-IN-9 hydrochloride, or their combination. Tumor tissues were analyzed using immunohistochemistry, and Western blotting to assess angiogenesis-associated markers, tissue hypoxia, and key molecular markers. Flow cytometry, ELISA, and immunostaining were performed to evaluate immune cell infiltration, cytokine expression, and the tumor immune microenvironment.</p><p><strong>Results: </strong>The combination of anlotinib and PD-1/PD-L1-IN-9 hydrochloride significantly inhibited tumor growth compared to monotherapy, associated with improved neovascularization and alleviated hypoxia. Combined therapy increased CD8+ T cell infiltration, reduced immunosuppressive cell populations, and partially modulated cytokine profiles, thereby enhancing the antitumor immune response.</p><p><strong>Conclusion: </strong>Anlotinib combined with PD-1/PD-L1-IN-9 hydrochloride exhibits superior antitumor efficacy in colorectal cancer compared to either agent alone, potentially by reshaping the tumor microenvironment. These findings support further exploration of combined anti-angiogenic and immune checkpoint therapy as a promising strategy for colorectal cancer treatment.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"597338"},"PeriodicalIF":4.1,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13327795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148377305","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":"T Helper Cells and Cytokine Networks in the Immunopathogenesis of Multiple Sclerosis.","authors":"Simeon Ikechukwu Egba, Gavin Chibundu Ikechukwu, Chinenye Iheanyi Okereke, Innocent Ogheneovo Orhonigbe, Robert Ikechukwu Uroko, Okechukwu Paul Chima Ugwu","doi":"10.2147/ITT.S607713","DOIUrl":"10.2147/ITT.S607713","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic autoimmune disorder of CNS with demyelination, neurodegeneration and compartmentalized inflammatory disorder. Excessive T-helper cell (CD4⁺) activation and unregulated cytokine signaling play a key role in its onset and progression. These changes impair communication between peripheral immune cells and CNS resident microglia, astrocytes and oligodendrocytes. This review provides an overview on the contribution of specific subsets of T-helper cells to MS pathology/immunity. Th1 cells release interferon-γ and lymphotoxin, that stimulate activation of myeloid cells/antigen presentation. Activated by IL-23, the Th17 cells produce IL-17A/F that lowers the blood-brain barrier (BBB) integrity, recruit neutrophils and monocytes, and enhance microglial killing. Activation of CD4⁺ T cells leads to activation of B cells via T follicular helper cells which couple these processes through the production of IL-21 and CXCR5. This leads to the development of tissue-like aggregates and intrathecal antibody production. T-cell plasticity adds to epitope spreading as well as chronic inflammation, IL-22, IL-9, IL-1β, IL-6, and TGF-β (these are additional mediators involved in the regulation of effector phenotypes). In MS, the regulation of dendritic cell co-stimulation and of glial activation often does not work. This is due to the lack of control of dendritic-cells co-stimulation and the lack of regulation of glial activation by regulatory pathways such as FOXP3⁺ regulatory T cells and Tr1 cells that secrete IL-10 and TGF-Beta. The review also explores the cytokine network biomarkers, CSF and serum signatures and single-cell immune states, as well as existing and new drugs. These include migration blockade, targeting of S1P-receptors, anti-CD20 therapy, targeting of Th17/GM-CSF and JAK-STAT pathways, low-dose IL-2, approaches of targeting antigens and engineered Tregs. Investigating the areas of stage and compartment-specific CD4⁺ T-cell circuits can help to advance targeted immunomodulation in progressive MS and neuro-repair.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"607713"},"PeriodicalIF":4.1,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13316819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148362690","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":"Irinotecan Modulates Immune Checkpoints in Neuroblastoma.","authors":"Tom Lapidus, Elina Zorde-Khvalevsky, Alaa Jolani, Gal Goldstein, Amnon Peled","doi":"10.2147/ITT.S598469","DOIUrl":"10.2147/ITT.S598469","url":null,"abstract":"<p><strong>Background: </strong>Neuroblastoma (NBL) is the most common extracranial solid tumor in children, with a 50% survival rate in high-risk cases. Chemotherapy combination with immunotherapy is central to HR-NBL treatment.</p><p><strong>Aim: </strong>This study aimed to explore how Irinotecan influences the immune landscape of NBL cells, particularly focusing on the modulation of immune checkpoints relevant to future chemo-immunotherapy strategies.</p><p><strong>Methods: </strong>Two neuroblastoma cell lines, SK-N-BE(2) and SH-SY5Y, were exposed to sub-lethal doses of Irinotecan and IFN-γ. Flow cytometry assessed the expression of immune markers, including GD2, CD47, MHC I, and PD-L1. We also examined phagocytosis by macrophages and T-cell-mediated killing. In vivo studies using a neuroblastoma mouse model assessed the effects of Irinotecan and PBMC injections. Soluble CD47 was also measured in cell culture supernatants and exploratory patient plasma samples.</p><p><strong>Results: </strong>Treatment exposure was associated with modulation of several immune-related markers, including GD2, CD47, PD-L1, and MHC class I. While Irinotecan reduced macrophage-mediated phagocytosis, this effect was reversed by the addition of anti-CD47 antibodies. T-cell-mediated killing was enhanced when NBL cells were pre-treated with Irinotecan. In vivo studies showed that the combination of PBMCs and Irinotecan resulted in reduced tumor burden compared to either treatment alone. Furthermore, CD47 expression was detectable in-patient plasma, suggesting that soluble CD47 may warrant exploration in larger future cohorts.</p><p><strong>Conclusion: </strong>This pilot study suggests that irinotecan may modulate key immune checkpoints in neuroblastoma. These results supports further investigation of rational chemo-immunotherapy combinations, including GD2 and CD47-targeted combination strategies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"598469"},"PeriodicalIF":4.1,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13271423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148273260","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":"Myeloid Cell-Derived Thrombospondin-1 Mediates Anti-Metastatic Effects of Histamine Dihydrochloride in B16 Melanoma.","authors":"Nuttida Issdisai, Mustafa Kaya, Kristoffer Hellstrand, Hanna Grauers Wiktorin, Anna Martner","doi":"10.2147/ITT.S596703","DOIUrl":"10.2147/ITT.S596703","url":null,"abstract":"<p><strong>Introduction: </strong>Histamine dihydrochloride (HDC) has been shown to reduce metastatic spread of tumors by modulating myeloid cells, including immunosuppressive monocytes. Thrombospondin-1 (TSP-1), a matricellular glycoprotein present in the pre-metastatic niche, has also been implicated in limiting tumor metastasis. Microarray analyses have identified <i>THBS1</i>, encoding TSP-1, as an HDC-induced gene in human myeloid cells. This study investigated the mechanisms underlying HDC-induced TSP-1 expression and assessed whether TSP-1 contributes to the anti-metastatic effects of HDC in melanoma progression.</p><p><strong>Methods: </strong>TSP-1 expression and secretion were analyzed in human and murine myeloid cell subsets following HDC stimulation. Patient datasets were used to assess the clinical relevance of <i>THBS1</i> expression in melanoma tissue. The functional significance of TSP-1 for HDC-mediated metastasis control was investigated in the B16F10 melanoma model of hematogenous lung metastasis in wild-type and TSP-1 knockout (KO) mice.</p><p><strong>Results: </strong>HDC robustly induced TSP-1 expression and secretion across multiple myeloid cell populations, including human and murine myeloid-derived suppressor cells. This effect was mediated via histamine type-2 receptors (H₂Rs) and downstream cAMP-PKA signaling. Analysis of human melanoma datasets revealed reduced <i>THBS1</i> expression in tumor tissue and an association between high <i>THBS1</i> expression and improved overall survival. In addition, <i>THBS1</i> expression correlated with the histamine synthesis gene histidine decarboxylase in human melanoma samples. In vivo, systemic HDC treatment increased lung TSP-1 levels and reduced pulmonary metastasis in wild-type but not in TSP-1 KO mice.</p><p><strong>Discussion: </strong>We identify TSP-1 as a downstream effector of HDC in myeloid cells and show that its induction is mediated by H₂R-dependent cAMP-PKA signaling. The association between <i>THBS1</i> expression and favorable survival in human melanoma supports a protective role for TSP-1. These findings suggest a previously unrecognized myeloid-cell mediated mechanism of HDC with potential relevance for metastasis control.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"596703"},"PeriodicalIF":4.1,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13251772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148228501","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}