ImmunoTargets and Therapy最新文献

{"title":"Targeting STING Signalling Polarizes Tumor-Associated Neutrophils to Boost Anticancer and Abscopal Antimetastatic Functions.","authors":"Alina Drzyzga, Justyna Czapla, Tomasz Cichoń, Sybilla Matuszczak, Ewelina Pilny, Magdalena Jarosz-Biej, Joanna Ciepła, Ryszard Smolarczyk","doi":"10.2147/ITT.S576457","DOIUrl":"10.2147/ITT.S576457","url":null,"abstract":"<p><strong>Introduction: </strong>The stimulator of interferon genes (STING) pathway has emerged as a promising target for cancer immunotherapy. Tumor-associated neutrophils (TANs) are underrated among the cells involved in STING-targeted therapies. The polarization state of TANs divides them into antitumor N1 and tumor-supportive N2 TANs. Our purpose was to assess whether STING activation stimulates the repolarization of TANs toward the N1 subtype and to investigate the potential participation of TANs in metastasis and macrophage polarization processes.</p><p><strong>Methods: </strong>This research was carried out on murine B16-F10 melanoma and 4T1 breast carcinomas. Flow cytometry, immunofluorescence microscopy, and multiplex immunoassay were used to assess the phenotype of TANs. Magnetic cell sorting was employed to assess the cytotoxic potential of TANs. The spontaneous 4T1 lung metastasis model enabled assessment of the impact of primary tumor targeting with STING agonist on the inhibition of metastasis and lung immune landscape changes. To verify the influence of in vivo cGAMP-activated TANs on the macrophages phenotype, the co-culture experiments of bone marrow-derived macrophages (BMDM) and TANs were conducted.</p><p><strong>Results: </strong>In both types of tumors, STING targeting converted TANs polarization state toward anticancer N1 subtype, marked by an increase in ICAM-1, CD69, Fas, CXCL10, TNFα, CCL3 expression, and a decrease in VEGF. Targeting STING induced a cytotoxicity of TANs against 4T1 cancer cells, while neutrophils masking revealed their importance for the maintenance of health conditions. Treatment of primary 4T1 tumors resulted in inhibition of metastasis and conversion of lung immune cells toward an anticancer phenotype. Direct co-cultivation of TANs derived from cGAMP-treated tumors with BMDM polarized them toward M1-like cells.</p><p><strong>Conclusion: </strong>Targeting STING provides polarization of TANs phenotype toward anticancer N1 subtype. Obtained data fills the gaps in the knowledge of the impact of STING-activating therapy on TANs functions, participation in the metastasis process, and acquisition of M1 phenotype by macrophages.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"576457"},"PeriodicalIF":4.1,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12927852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147285312","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 Dual Mechanism of Action of CO-005 Overcomes CD20 Resistance in Diffuse Large B-Cell Lymphoma.","authors":"Sittana Matar, Seham Skah, Liza E B Moltu, Øystein Åmellem, Hanne R Hagland, Kjetil Hestdal, Rolf D Pettersen, Nina Richartz","doi":"10.2147/ITT.S572396","DOIUrl":"10.2147/ITT.S572396","url":null,"abstract":"<p><strong>Purpose: </strong>Despite the clinical success of anti-CD20 monoclonal antibodies (mAbs) such as rituximab in the treatment of B-cell lymphoma, therapeutic resistance and relapse remain significant challenges, particularly in tumors with low or heterogeneous CD20 expression resulting from antigen loss or phenotypic shifts. To address this limitation, new therapeutic strategies are needed that act independently of CD20 while maintaining robust immune effector engagement. CO-005 is a humanized anti-CD47 fusion protein designed to simultaneously disrupt the CD47-SIRPα checkpoint and induce direct programmed cancer cell death (PCCD) distinct from other anti-CD47 agents.</p><p><strong>Methods: </strong>The capacity of therapeutic mAbs to induce PCCD was assessed in lymphoma cell lines by flow cytometric detection of cell death and apoptotic markers. Antibody binding, phagocytic activity, and mechanistic analyses assessed intracellular signaling events associated with PCCD were measured by flow cytometry following treatment. The antitumor activity of CO-005 was evaluated in NOD-scid IL2Rγnull (NSG) mice bearing subcutaneous lymphoma xenografts, with efficacy and survival outcomes assessed for CO-005 as monotherapy and in combination with rituximab.</p><p><strong>Results: </strong>CO-005 demonstrated potent and durable antitumor activity across multiple lymphoma xenograft models, including rituximab-resistant tumors model. CO-005 shares key mechanistic features with therapeutic anti-CD20 antibodies independent of CD20 signaling, including the induction of type III programmed cell death via receptor capping, calcium flux, reactive oxygen species generation, and actin cytoskeleton dependence, accompanied by surface calreticulin exposure. In vivo, CO-005 triggered robust intratumoral PCCD and remodelled the tumor microenvironment, characterized by increased macrophage and neutrophil infiltration, thereby enhancing innate immune activation and supporting a dual-mechanism mode of action that couples direct cancer cell killing with myeloid engagement.</p><p><strong>Conclusion: </strong>These findings position CO-005 as a mechanistically distinct and immunologically active therapeutic with the potential to overcome limitations of both CD20- and CD47-directed therapies and expand treatment options for B-cell lymphoma.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"572396"},"PeriodicalIF":4.1,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12927799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147285250","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 Comparative Effectiveness of Enlonstobart and Camrelizumab as Second-Line Recurrent or Metastatic Cervical Cancer Therapies: Matching-Adjusted and Simulated Treatment Comparisons.","authors":"Huiqiao Gu, Bingxin Hu, Yawen Jiang","doi":"10.2147/ITT.S572970","DOIUrl":"10.2147/ITT.S572970","url":null,"abstract":"<p><strong>Purpose: </strong>Recurrent or metastatic cervical cancer (R/M CC) has limited therapeutic options after first-line treatment failure. Both enlonstobart and camrelizumab are anti-PD-1 antibodies recommended for second-line treatment, but direct comparative evidence is lacking. This study aimed to evaluate the relative efficacy of enlonstobart versus camrelizumab as second-line treatments in patients with R/M CC.</p><p><strong>Methods: </strong>We conducted an unanchored matched-adjusted indirect comparison (MAIC) using individual patient data from the single-arm enlonstobart Phase II trial and published aggregate data from the camrelizumab phase II trial, both of which targeted an R/M CC population with prior platinum-based treatment failure. Entropy balancing was used to adjust for eight baseline covariates. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Cox proportional hazards models were used to estimate hazard ratios (HRs) for the survival endpoints. A simulated treatment comparison (STC) was performed as sensitivity analysis.</p><p><strong>Results: </strong>Before adjustment, no significant differences were observed between treatments for OS or PFS. After MAIC adjustment, enlonstobart demonstrated significant OS advantage over camrelizumab (HR=0.51, 95% CI 0.27-0.94, p=0.03), with median OS of 32.2 versus 14.94 months. PFS showed a favorable trend but was not statistically significant (HR=0.69, 95% CI 0.42-1.14, p=0.15). STC analysis corroborated the OS benefit and suggested significant PFS advantage of enlonstobart over camrelizumab. Safety profiles were comparable between treatments.</p><p><strong>Conclusion: </strong>This indirect comparison demonstrated that enlonstobart provided a significant OS advantage compared to camrelizumab in patients with second-line R/M CC. These findings suggest enlonstobart may represent a promising therapeutic option for PD-(L)1 positive R/M CC patients.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"572970"},"PeriodicalIF":4.1,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12929208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147291276","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":"Immune Microenvironment of Hair Follicles in Tumor Immunotherapy.","authors":"Bo Li, Sitong Jiang, Fan Yang, Min Tang, Haozhen Lv, Lin Li, Jianmin Chang","doi":"10.2147/ITT.S554731","DOIUrl":"10.2147/ITT.S554731","url":null,"abstract":"<p><p>Although tumor immunotherapy has shown significant efficacy against solid tumors, it frequently causes cutaneous and follicular adverse events resulting from disruption of the hair follicle immune microenvironment. This microenvironment is maintained through careful regulation by immune cells and cytokine networks to support normal hair cycling. Immune checkpoint inhibitors disturb this balance by activating T cells, promoting macrophage polarization toward pro-inflammatory phenotypes, upregulating inflammatory cytokines such as tumor necrosis factor-alpha, and activating Toll-like receptor/nuclear factor-kappa B signaling pathways, ultimately leading to follicular toxicity including alopecia. Encompass relies mainly on topical corticosteroids and other immunomodulatory agents. A deeper understanding of these mechanisms is essential to identify key regulatory nodes for future targeted interventions.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"554731"},"PeriodicalIF":4.1,"publicationDate":"2026-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12927823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147285214","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":"Recent Advances in Vitiligo Treatment.","authors":"Ye Qiu, Xiangxi Su, Jingru Chen, Shaojing Jiang, Xinrui Tang, Yurong He, Fang Liu","doi":"10.2147/ITT.S577653","DOIUrl":"10.2147/ITT.S577653","url":null,"abstract":"<p><strong>Purpose: </strong>This review systematically summarizes breakthrough advances in vitiligo treatment from 2020 to 2025 to provide the latest evidence-based insights for clinical practice.</p><p><strong>Patients and methods: </strong>We searched ClinicalTrials.gov and PubMed for literature and clinical trials published within this period. Inclusion criteria encompassed randomized controlled trials (RCTs), Phase II and above clinical trial results, and fundamental research with clear clinical translational value.</p><p><strong>Results: </strong>Our analysis identified that JAK inhibitors achieved significant repigmentation by blocking the IFN-γ/JAK-STAT signaling pathway, while novel agents such as IL-15 inhibitors selectively eliminated pathogenic CD8⁺ T cells, suppressing immune-mediated damage at its source. The combination of 308 nm excimer laser with JAK inhibitors or platelet-rich plasma (PRP) increased repigmentation rates in acral lesions to 56.1%, and vitamin D adjunct therapy demonstrated synergistic effects. For stable disease, ReCell technology combined with narrowband UVB (NB-UVB) emerged as an effective option, whereas miniature punch grafting further optimized surgical outcomes. Additionally, repurposed traditional drugs and antioxidant strategies expanded the available clinical arsenal.</p><p><strong>Conclusion: </strong>Vitiligo treatment has entered an era of precision immune modulation, with JAK inhibitors establishing themselves as first-line therapy and novel biologics showing significant promise. Combined phototherapy and cellular therapy innovations markedly enhance repigmentation efficiency, and drug repurposing continues to enrich the therapeutic landscape.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"577653"},"PeriodicalIF":4.1,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13044860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147623890","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":"Enhancing NK Cell Activity in Colorectal Cancer with an Fc-Optimized Antibody Targeting CD276 (B7-H3).","authors":"Sylwia A Stefańczyk, Xenija Kaiser, Ilona Hagelstein, Martina S Lutz, Samuel J Holzmayer, Latifa Zekri, Melanie Märklin, Susanne Jung","doi":"10.2147/ITT.S533342","DOIUrl":"10.2147/ITT.S533342","url":null,"abstract":"<p><strong>Background & aims: </strong>Colorectal cancer (CRC) represents a major global health burden due to its high incidence and mortality, particularly in the advanced stages, with limited treatment options. While therapies that block the PD-1/PD-L1 pathway have demonstrated clinical benefit, their success in CRC is largely confined to patients with high microsatellite instability (MSI-H) tumors. Innovative immunotherapeutic solutions are critically needed for the majority of CRC cases. CD276 (B7-H3), a B7 family immune checkpoint molecule, is overexpressed in many cancers including CRC. Significant CD276 upregulation in CRC cell lines compared to benign tissues has been previously demonstrated. In this study, the potential of an Fc-optimized anti-CD276 monoclonal antibody to enhance natural killer (NK) cell activity in CRC was evaluated.</p><p><strong>Methods: </strong>An Fc-optimized monoclonal antibody, 8H8_SDIE, was developed to enhance NK cell activity by increasing CD16 binding. In vitro experiments were conducted using human CRC cell lines and peripheral blood mononuclear cells (PBMCs) from healthy adult donors to evaluate the binding specificity of 8H8_SDIE to CD276. NK cell activation was assessed by measuring the upregulation of activation markers (CD69, CD25, and CD107a) and secretion of cytotoxic mediators (IFNγ, granzyme B, and perforin). Cytotoxicity assays were performed to determine NK cell-mediated tumor cell lysis.</p><p><strong>Results: </strong>8H8_SDIE specifically bound to CD276-positive CRC cells and significantly enhanced NK cell activation. These effects included increased levels of activation and cytotoxic mediators. In cytotoxicity assays, 8H8_SDIE demonstrated potent NK cell-mediated lysis of CRC cells.</p><p><strong>Conclusion: </strong>The Fc-optimized anti-CD276 antibody 8H8_SDIE effectively enhanced NK cell reactivity against CD276-positive CRC cells and induced tumor cell lysis in vitro. These findings suggest that 8H8_SDIE holds potential as a novel immunotherapeutic candidate for CRC, particularly for patients with microsatellite-stable disease, and warrants further evaluation in advanced preclinical and future clinical studies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"533342"},"PeriodicalIF":4.1,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12912133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146221381","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 Novel Prognostic Signature Composed of Autophagy and Liver Metastasis in Colorectal Cancer: Comprehensive Analysis of Bulk and Single-Cell Transcriptomic Data.","authors":"Binglong Bai, Yuekai Cui, Xihao Zhong, Bingzi Zhu, Ziqi Meng, Letian Chen, Leyan Di, Linjing Huang, Jisheng Wang, Zhouxiang Jin, Xufeng Lu, Bin Zhou","doi":"10.2147/ITT.S563779","DOIUrl":"10.2147/ITT.S563779","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a highly aggressive malignancy prone to liver metastasis, which significantly worsens prognosis of patients. Autophagy supports tumor cell survival by meeting metabolic demands and evading programmed cell death. This study aimed to develop a prognostic risk signature for CRC patients by integrating autophagy- and metastasis-related genes and to investigate its association with the tumor immune microenvironment and implications for immunotherapy.</p><p><strong>Methods: </strong>Weighted gene co-expression network analysis (WGCNA) identified candidate genes related to autophagy and liver metastasis. Univariate Cox and LASSO regression analyses were employed to develop a risk signature in the TCGA cohort, which was subsequently validated using an independent GEO cohort. Functional enrichment, immune infiltration, the heterogeneity and dynamics of macrophages and <i>CD8⁺</i> T cells, and cell-cell communication were analyzed. The expression patterns of key genes were confirmed through Western blotting and immunohistochemistry.</p><p><strong>Results: </strong>A prognostic risk signature incorporating six biomarkers (<i>SPP1</i>, <i>JCHAIN</i>, <i>DNASE1L3</i>, <i>SNAI1</i>, <i>TPM1</i>, and <i>FKBP10</i>) was developed and confirmed. The risk signature was an independent prognosticator and outperformed traditional prognostic factors. The patients in high-risk group exhibited heightened Tumor Immune Dysfunction and Exclusion (TIDE) scores, indicating a potential for immunotherapy resistance. Furthermore, enhanced autophagy and metastatic activity were accompanied by differentiation of macrophages toward an <i>SPP1⁺</i> M2-like phenotype and of <i>CD8⁺</i> T cells toward an exhausted state. Experimental validation confirmed that <i>SPP1</i>, <i>SNAI1</i>, and <i>FKBP10</i> were highly expressed in CRC tissues.</p><p><strong>Conclusion: </strong>In our study, we developed and validated a novel autophagy- and liver metastasis-associated prognostic signature for CRC. The risk signature effectively predicts alterations in the tumor immune microenvironment, immunotherapy, chemotherapy sensitivity and intercellular communication across different risk groups. Importantly, our findings reveal that autophagy and liver metastasis synergistically foster an immunosuppressive microenvironment, highlighting a potential target for therapeutic intervention.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"563779"},"PeriodicalIF":4.1,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147594662","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":"Postural Orthostatic Tachycardia Syndrome, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID as Neuroimmune Disorders.","authors":"Svetlana Blitshteyn, Taylor A Doherty, Lawrence Steinman","doi":"10.2147/ITT.S581262","DOIUrl":"10.2147/ITT.S581262","url":null,"abstract":"<p><p>Postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID are heterogeneous disorders with overlapping complex, multi-factorial and multi-systemic pathophysiology. POTS and ME/CFS are the most common phenotypes of Long COVID that can lead to significant disability and functional impairment. The exact pathophysiologic mechanisms of these disorders alone or in combination are still being investigated, but important mechanistic factors have been identified, such as autonomic dysfunction, immune dysregulation, autoimmunity, mitochondrial dysfunction, cerebral hypoperfusion, and neuroinflammation. To this end, we believe that these conditions should be viewed as neuroimmune disorders and should be included in the field of neuroimmunology, with its educational curriculum, training, and clinical care pathways. Including these disorders as part of neuroimmunology subspecialty is the key to advancing the science and clinical care of this underserved patient population with these complex and disabling conditions.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"581262"},"PeriodicalIF":4.1,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12998959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487675","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":"Emerging Predictive Biomarkers of Immunotherapy Sensitivity in Patients with Non-Small Cell Lung Cancer.","authors":"Eleonora Gariazzo, Francesca Colamartini, Martina Ubaldi, Valentina Santo, Leonardo Brunetti, Chiara Tomarelli, Daniele Ognissanti, Jouana Nassar, Silvia Costabile, Luca Romano, Emanuela De Vita, Ilenia Scorpiniti, Miriam Macrì, Roberta Porreca, Maria Francesca Currà, Alessio Cortellini, Biagio Ricciuti, Giulio Metro","doi":"10.2147/ITT.S567238","DOIUrl":"10.2147/ITT.S567238","url":null,"abstract":"<p><p>In recent years, the therapeutic landscape of non-small cell lung cancer (NSCLC) has been transformed by immune checkpoint inhibitors (ICIs), which have led - in some patients - to unprecedented survival expectancy. Nevertheless, identifying patients most likely to benefit from ICI remains a major challenge. While PD-L1 expression and tumor mutation burden (TMB) represent established predictive biomarkers, their predictive ability still needs to be improved, which underscores the need for identifying additional (bio)markers for treatment selection. Recent research has highlighted multiple emerging biomarkers, including genomic alterations (eg, <i>KEAP1, STK11, SMARCA4</i>), markers of metabolic pathway dysregulation (IDO, adenosine axis), tumor-infiltrating lymphocytes, and blood-based biomarkers (eg soluble markers of inflammation, germline HLA diversity, and circulating tumor DNA). Host-related determinants, such as the history of tobacco exposure and the body mass index, further contribute to immunotherapy outcomes. In addition, artificial intelligence (AI) and machine learning (ML) approaches are enabling integration of multidimensional data, leading to predictive scoring systems which have outperformed conventional biomarkers in certain settings. This review synthesizes current evidence on established and emerging predictive biomarkers in NSCLC, highlighting the potential of combining biological, host, and computational features to inform precision immunotherapy strategies.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"567238"},"PeriodicalIF":4.1,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13008126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515423","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":"Enhancing Anti-CTLA-4 Antibody Delivery to the Brain Using Focused Ultrasound and Microbubbles.","authors":"Maria Afonso Pereira, Vanessa Drevenakova, Qiyixing Ethan Liu, Sarina Grewal, Sophie V Morse","doi":"10.2147/ITT.S569804","DOIUrl":"10.2147/ITT.S569804","url":null,"abstract":"<p><strong>Introduction: </strong>Gliomas, particularly glioblastomas, are characterised by their poor prognosis and low patient survival rate. Cytotoxic T lymphocyte-associated antigen-4 antibodies, a type of immune checkpoint inhibitor, have shown promise as an effective treatment strategy against the most aggressive tumour cells within the microenvironment of gliomas. However, their delivery to the brain is hindered by the blood-brain barrier, which is leaky in a heterogenous way, leading to uneven drug distribution across the tumour. Focused ultrasound, combined with intravenously administered microbubbles, is a technique that can non-invasively, safely, and reversibly increase the permeability of the blood-brain barrier in a targeted area, promoting the delivery of therapeutics, such as immune checkpoint inhibitors, to inaccessible tumour areas and thereby helping to prevent tumour relapse.</p><p><strong>Methods: </strong>We applied two different types of focused ultrasound sequences (long pulses vs rapid short-pulses) with microbubbles to the left hippocampus of wild-type female C57BL/6 mice before administering fluorescently labelled cytotoxic T lymphocyte-associated antigen-4 antibodies.</p><p><strong>Results: </strong>We determined that the targeted brain region had a significant increase in antibody delivery following ultrasound treatment with both pulse sequences. A more uniform delivery was achieved when treating with rapid short-pulse sequences (<i>p-value</i> = 0.0130), where bursts of short 5 µs pulses of focused ultrasound were emitted at a fast repetition frequency (1.25 kHz). We observed a significant increase in anti-tumour immune cells in long-pulse treated brains (<i>p-value</i> = 0.0021 (CD3⁺ cells) and <i>p-value</i> = 0.0001 (MHC class II⁺ cells)).</p><p><strong>Conclusion: </strong>These results provide a proof-of-principle for how focused ultrasound with microbubbles can promote homogenous anti-tumour drug delivery and modulate the immune microenvironment.</p>","PeriodicalId":30986,"journal":{"name":"ImmunoTargets and Therapy","volume":"15 ","pages":"569804"},"PeriodicalIF":4.1,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515374","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}