Cancer immunology, immunotherapy : CII最新文献

{"title":"Broader gene representation by whole-exome sequencing improves accuracy of tumor mutational burden assessment for selection of pembrolizumab immunotherapy.","authors":"Milan Radovich, James Wacker, Jeffrey Solzak, Hongseok Tae, Jennifer R Ribeiro, Todd Maney, Bradley Hancock, James Hamrick, George W Sledge, Manmeet S Ahluwalia, Stephen V Liu, Emil Lou, Vivek Subbiah, Balazs Halmos, Daniel Magee, David B Spetzler","doi":"10.1007/s00262-026-04365-4","DOIUrl":"10.1007/s00262-026-04365-4","url":null,"abstract":"<p><p>Although the tissue-agnostic FDA approval of pembrolizumab for tumor mutational burden (TMB)-high tumors has provided meaningful clinical benefit to patients, there remains a need to optimize TMB assessment. In this cohort study, we investigated the discordance between whole-exome sequencing (WES) and panel-based methods and evaluated their relative clinical utility in identifying patients likely to benefit from pembrolizumab. Molecularly-profiled tumors from patients treated with pembrolizumab were analyzed (N = 26,756). TMB was calculated using WES data or panels of genes (324, 523, and 648) from commercially available assays (TMB-High ≥ 10 mutations/Mb). Pembrolizumab-specific overall survival (OS) was calculated from insurance claims data (treatment start to last contact). Targeted gene panels tended to overestimate TMB and demonstrated ~ 10-15% discordance in binary TMB calls from WES, which was most pronounced for the smallest panel. Discordant cases for all three panels clustered near the TMB clinical calling threshold. WES offered improved stratification of patients for pembrolizumab treatment: in a subset of \"TMB-reliant\" tumor types lacking disease-specific immune checkpoint inhibitor (ICI) indications (n = 3,981), median OS was approximately 5 months longer for cases identified as WES-TMB-High but panel-TMB-Low compared to those identified as WES-TMB-Low but panel-TMB-High (p < 0.05 for 324-gene and 648-gene panels). Approximately, 10-11% of patients were potentially misclassified by panels. These findings emphasize the importance of broader gene representation for accurate TMB determination near the clinical threshold-especially in tumor types lacking disease-specific ICI indications, where tissue-agnostic MSI-High/dMMR or TMB-High labeling represents the principal on-label route to ICI therapy.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13161441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147871331","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":"Mechanical preconditioning by shear stress enhances memory formation and anti-tumor function of CAR-T cells.","authors":"Lianfeng Zhao, Jiaqi Liu, Yan Zhang, Xinhao Yang, Tianyu Chen, Xinyang Xu, Muya Zhou, Zhigang Hu, Zhigang Guo","doi":"10.1007/s00262-026-04391-2","DOIUrl":"10.1007/s00262-026-04391-2","url":null,"abstract":"<p><p>Chimeric antigen receptor T-cell (CAR-T) therapy has achieved remarkable success in the treatment of hematological malignancies, and its application to solid tumors is currently under active investigation. Upon infusion into the bloodstream, CAR-T cells are exposed to fluid shear stress (SS) generated by blood flow. However, the impacts of SS on CAR-T cells function are not well understood. In this study, we exposed anti-mesothelin (MSLN) CAR-T cells to a shear stress of 5 dynes/cm2, and observed reduced cell viability, enhanced activation, and decreased expression of exhaustion markers. Notably, we found that a one-hour SS stimulation applied seven days after T cell isolation and activation significantly increased the proportion of stem cell memory T cells (Tscm), mitigated exhaustion, and enhanced the anti-tumor efficacy of anti-MSLN CAR-T cells. Furthermore, SS-preconditioned CAR-T cells exhibited resistance to SS-induced cell death and demonstrated increased migratory capacity. In vivo experiments, SS-preconditioned CAR-T cells exhibited greater tumor infiltration, improved persistence, superior tumor control, and a favorable safety profile in tumor-bearing mice. Transcriptomic analysis revealed upregulation of genes associated with activation, infiltration, and microtubule dynamics, alongside downregulation of genes linked to exhaustion, apoptosis, and immunosuppression. Collectively, our findings demonstrate for the first time that mechanical preconditioning with fluid shear stress can reprogram CAR-T cells toward a more functional and persistent phenotype, offering a novel strategy to optimize CAR-T therapy for solid tumors.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13341982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147871314","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":"Cabozantinib and atezolizumab for recurrent or metastatic esophageal squamous cell carcinoma after platinum-based chemotherapy failure: a single-arm phase II study and biomarker analysis.","authors":"Hung-Yang Kuo, Ta-Chen Huang, Chien-Huai Chuang, Tsung-Che Wu, Yen-Lin Huang, Chia-Chi Lin, Jang-Ming Lee, Jhe-Cyuan Guo, Chih-Hung Hsu","doi":"10.1007/s00262-026-04408-w","DOIUrl":"10.1007/s00262-026-04408-w","url":null,"abstract":"<p><strong>Purpose: </strong>Anti-PD-1 immune-checkpoint inhibitors (ICIs) are approved for treating patients with recurrent or metastatic (R/M) esophageal squamous cell carcinoma (ESCC) who have failed platinum-based chemotherapy. However, their efficacy as monotherapy remains limited. We hypothesized that adding cabozantinib, a multikinase inhibitor with antiangiogenic and immunomodulatory properties, could enhance the therapeutic efficacy of atezolizumab, an anti-PD-L1 ICI, in patients with R/M ESCC.</p><p><strong>Patients and methods: </strong>A single-arm, single-institution phase II trial was conducted (NCT05007613) that included patients with ESCC who experienced disease progression following a platinum-based chemotherapy for R/M ESCC or within 6 months after chemo(radio)therapy for locoregional disease. Participants received cabozantinib 40 mg daily and atezolizumab 1200 mg every 3 weeks until disease progression or intolerable toxicity was reached. The primary endpoint was investigator-assessed objective response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity profile.</p><p><strong>Results: </strong>Between June 2021 and March 2024, 24 patients were enrolled in this study. With a median follow-up of 7.0 months (range, 0.5-38.1), 7 patients achieved partial responses and 7 had stable disease. The ORR was 29.1% (95% CI = 11.7%-60.1%), and the disease control rate (DCR) was 58.3% (95% CI = 31.9-97.9%). The median duration of response was 6.5 months (95% CI = 0.9-12.1), the median PFS was 2.2 months (95% CI = 0.64-3.76), and the median OS was 7 months (95% CI = 2.36-11.64). Of the 24 patients, 12 (50%) experienced ≥ grade 3 treatment-related adverse events. Patients with high PD-L1 expression and increased intratumoral or stromal CD8+ tumor infiltrating lymphocytes had numerically higher ORR and improved OS.</p><p><strong>Conclusion: </strong>The combination of cabozantinib and atezolizumab has an acceptable safety profile and moderate antitumor activity as a second-line treatment for patients with R/M ESCC.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864913","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":"Novel recombinant protein PK5-Gal-3C enhances the anti-tumor activity of T cells via binding with TRPV2.","authors":"Guopeng Zhang, Wei Zhang, Xiaohuan Wei, Zhenyu Wang, Feitong Wang, Shishuo Sun, Haiheng Xu, Xiangye Liu, Qing Zhang, Xiaoge Gao","doi":"10.1007/s00262-026-04401-3","DOIUrl":"10.1007/s00262-026-04401-3","url":null,"abstract":"<p><p>Investigating strategies to enhance T cell effector function can improve the adoptive immune responses to tumors and complement existing tumor immunotherapies. Here, we present a novel artificially designed recombinant protein, PK5-Gal-3C, which is composed of the fifth kringle domain of plasminogen (PK5) and the C-terminal carbohydrate-recognition domain of galectin-3 (Gal-3C). This protein exhibited potent anti-tumor activity by significantly enhancing T cell effector function. Specifically, PK5-Gal-3C directly activated T cells by binding to glycosylated TRPV2 via Gal-3C, a thermosensitive calcium-permeable cation channel, thereby promoting the influx of calcium ions to enhance T cells cytotoxicity via the activation of c-Jun. Correspondingly, inhibition of TRPV2 or c-Jun impaired the cytotoxicity of T cell mediated by PK5-Gal-3C. Additionally, PK5-Gal-3C demonstrated significant anti-tumor activity by enhancing T cell tumor infiltration and cytotoxicity in a mouse model, as well as improving the anti-tumor efficacy of CAR-T cells in solid tumors. In summary, PK5-Gal-3C is a safe and potent anti-tumor agent with promising potential for T cell-mediated cancer immunotherapy.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147849025","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":"β-elemene enhances the efficacy of PD-L1 inhibitor in lung cancer by reprogramming tumor-associated macrophages to M1 phenotype via suppressing FLT1/PI3K/AKT signaling.","authors":"Jianmin Wang, Yongxin Yu, Fenglin Lin, Hang Wang, Weiqi Nian","doi":"10.1007/s00262-026-04386-z","DOIUrl":"10.1007/s00262-026-04386-z","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICI), epitomized by PD-1/PD-L1 antibodies, have ushered in a new era in lung cancer treatment. However, ICI monotherapy is only applicable to a small subset of patients with high PD-L1 expression, while most patients with low expression require combination therapies. In this study, we found that β-elemene promotes M1 polarization of tumor-associated macrophages (TAMs) and enhances the efficacy of PD-L1 antibody (aPD-L1) in C57BL/6 mice. RNA sequencing and surface plasmon resonance revealed that β-elemene directly binds to FLT1 and inhibits the PI3K/AKT/FOXO1 signaling pathway, thereby mediating TAMs M1 polarization. Using Flt1 knockout mice, we further validated the critical role of Flt1 in TAMs polarization and confirmed that M1 polarization synergizes with aPD-L1 treatment. Furthermore, co-immunoprecipitation showed that the FLT1 intracellular domain binds to and phosphorylates the p85α subunit, triggering downstream signaling cascades. These findings elucidate the synergistic mechanism between β-elemene and aPD-L1. Moreover, given the clinical availability of both agents, they provide a strong rationale for further clinical evaluation of this combination therapy.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857754","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":"αTrop2/αCD3 bispecific protein engager-armed T cells (BATs) exhibit potent antitumor activity against nasopharyngeal carcinoma.","authors":"Kwanpirom Suwanchiwasiri, Chalermchai Somboonpatarakun, Nan Chaiyariti, Utid Suriya, Surang Chankhamhaengdecha, Pa-Thai Yenchitsomanus, Tavan Janvilisri, Mutita Junking","doi":"10.1007/s00262-026-04406-y","DOIUrl":"10.1007/s00262-026-04406-y","url":null,"abstract":"<p><p>Nasopharyngeal carcinoma (NPC) remains a highly aggressive malignancy with poor outcomes in advanced and recurrent disease. Although immune checkpoint inhibitors combined with chemotherapy improve survival, many patients still experience relapse or disease progression. Here, we developed a non-genetically modified cellular immunotherapy based on αTrop2/αCD3 bispecific protein engager-armed T cells (αTrop2/αCD3-BATs), targeting Trop2, which is highly expressed in NPC and minimally expressed in normal tissues. Molecular dynamics simulations supported stable dual binding of the BiPE to Trop2 and CD3ε, consistent with effective immune synapse formation. Functionally, αTrop2/αCD3-BATs exhibited potent, antigen-dependent cytotoxicity against Trop2-positive NPC cell lines (TW01, HK1, and CNE1) in both two-dimensional co-culture and three-dimensional spheroid models while sparing Trop2-negative cells. Target engagement induced robust T cell activation and proliferation, accompanied by increased expression of effector molecules such as FasL and elevated secretion of cytolytic mediators (perforin, granzymes, and granulysin) and pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-2). Collectively, these findings demonstrate that αTrop2/αCD3-BATs mediate potent and selective antitumor activity and support their further preclinical development as an MHC-independent cellular immunotherapy for Trop2-positive NPC.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147849028","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":"Correction: Thymic epithelial tumors at the crossroads of immunity, autoimmunity, and immunotherapy.","authors":"Kübra Canaslan, Fatemeh Moeini Nia, Maria Baez, Hassan Abolhassani, Natalie Ridge, Maroun Bou Zerdan, Jennifer Marks, Hussain Rangoonwala, Behnaz Jahanbin, Amir Hossein Emami, Katie O'Reilly, Yesim Gökmen-Polar, Sunil S Badve, Chunwei Xu, Yue Hao, Aparna Sharma, Swasthik Upadhya, Francoise Galateau Salle, Kelsey Pan, Badi El Osta, Dong M Shin, Fatemeh Ardeshir-Larijani","doi":"10.1007/s00262-026-04407-x","DOIUrl":"10.1007/s00262-026-04407-x","url":null,"abstract":"","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848965","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":"Rosuvastatin enhances the efficacy of venetoclax-azacitidine in older acute myeloid leukemia patients via reducing T-cell exhaustion.","authors":"Yuanmei Zhai, Yehua Yu, Renjun Bao, Jiajia Liu, Jianguo Fang, Wei Lu, Difan Zhang, Hezhou Guo, Yonghua Yao, Jun Shi","doi":"10.1007/s00262-026-04397-w","DOIUrl":"10.1007/s00262-026-04397-w","url":null,"abstract":"<p><p>Venetoclax plus hypomethylating agents (HMAs) is a standard therapy for older or unfit patients with acute myeloid leukemia (AML); however, some patients exhibit suboptimal responses, potentially associated with T-cell exhaustion. Our preclinical findings that statins enhance HMA efficacy by boosting anti-tumor T-cell responses prompted us to translate this strategy to the clinic. A multicenter phase II clinical trial (ChiCTR 2500111931) was conducted to evaluate the efficacy and safety of adding rosuvastatin to venetoclax and azacitidine (venetoclax-azacitidine) in older/unfit AML patients. After induction therapy with this triple combination, the cohort achieved a complete response (CR) rate of 55.5% and a composite complete remission (CRc) rate of 72.2%. Among patients who achieved CRc, 84.6% attained measurable residual disease (MRD) < 10^-3. With a median follow-up of 10 months, the median overall survival (OS) and relapse-free survival (RFS) were 18 and 14 months, respectively. Although no significant changes in lipid profiles were observed, multiparametric flow cytometry revealed significant reductions in PD-1⁺CD4⁺ T cells (p = 0.0137) and PD-1⁺CD8⁺ T cells (p = 0.0277) after therapy. In vitro experiments revealed that the addition of rosuvastatin diminished both early (PD-1⁺TIM-3⁻) and terminally (PD-1⁺TIM-3⁺) exhausted T cells, suggesting it prevents the development of T-cell exhaustion induced by venetoclax-azacitidine. Furthermore, functional assays confirmed that rosuvastatin addition significantly enhanced T cell cytotoxicity against leukemia cells. Collectively, our findings suggest that adding rosuvastatin to venetoclax-azacitidine shows preliminary clinical activity and acceptable safety, possibly by reducing T-cell exhaustion, thus supporting further study of this triple regimen in older/unfit AML patients.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147849014","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":"Artificial intelligence-powered H&E-based quantification of spatial tumor-infiltrating lymphocyte distribution identifies prognostic immune niches in colorectal cancer.","authors":"Hyun-Hee Koh, Seungeun Lee, Chiyoon Oum, Sanghoon Song, Soo Ick Cho, Sérgio Pereira, Chang Ho Ahn, Jun Yong Kim, Milim Kim, Minsun Jung","doi":"10.1007/s00262-026-04409-9","DOIUrl":"10.1007/s00262-026-04409-9","url":null,"abstract":"<p><strong>Purpose: </strong>The prognostic significance of tumor-infiltrating lymphocytes (TILs) in colorectal cancer (CRC) is well established; however, existing approaches inadequately capture their spatial distribution. We investigated the prognostic implications of TIL spatial distribution in CRC using an artificial intelligence (AI)-based method.</p><p><strong>Methods: </strong>A total of 202 patients with stage II-III CRC were included. TIL densities in intratumoral (iTIL) and stromal (sTIL) regions were quantified using AI-based analysis of hematoxylin and eosin (H&E)-stained images. Based on proximity to the tumor-stromal border (TSB), TILs were subclassified into core iTIL, bounding iTIL, bounding sTIL, and outermost sTIL. Immunoscore was calculated from CD3⁺ and CD8⁺ T-cell densities in the tumor center and invasive margin.</p><p><strong>Results: </strong>Correlations between AI-based and pathologist assessments (iTIL: r = 0.57; sTIL: r = 0.70) were comparable to inter-pathologist correlations (iTIL: r = 0.47; sTIL: r = 0.70). In univariate Cox regression analysis, bounding iTIL, bounding sTIL, and outermost sTIL were significantly associated with recurrence-free survival (RFS), whereas core iTIL was not. Composite TIL and TSB scores were developed by incorporating the prognostically significant regions. In multivariable analysis, the TIL score (p = 0.001), TSB score (p < 0.001), and Immunoscore (p < 0.001) independently predicted RFS. In microsatellite instability-high tumors, only the TSB score remained prognostically significant.</p><p><strong>Conclusion: </strong>AI-powered spatial analysis of TILs, particularly the TSB score, demonstrated prognostic performance comparable to conventional Immunoscore, thereby supporting the value of spatial immune profiling and AI-driven analysis of H&E-stained slides for improved risk stratification in CRC.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848984","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":"Dual-modality imaging enables longitudinal biodistribution profiling of intracerebroventricular CAR-T therapy in orthotopic glioma.","authors":"Chunzhao Li, Peng Zhang, Xiaobin Zhao, Rui Feng, Na Xian, Gangxiong Huang, Wenju Jiang, Zhenhua Hu, Yang Zhang, Nan Ji","doi":"10.1007/s00262-026-04403-1","DOIUrl":"10.1007/s00262-026-04403-1","url":null,"abstract":"<p><p>Locoregional CAR-T delivery is increasingly explored for glioblastoma to improve intracranial tumor exposure; however, organ-level biodistribution kinetics after intracranial administration remain poorly quantified in vivo, limiting route-informed optimization and preclinical risk assessment. Here, we report a dual-modality cell labeling and tracking strategy based on indocyanine green-conjugated iron nanoparticles (ICG-NPs) for in vivo assessment of B7-H3-targeting CAR-T cell (TX103) biodistribution using second near-infrared window (NIR-II) fluorescence imaging and magnetic resonance imaging (MRI). Using a heparin-protamine-assisted protocol, TX103 cells were labeled with high efficiency (83.1%) without detectable changes in viability, CAR expression, immunophenotype (including activation/exhaustion marker profile and CXCR3 expression), or cytotoxic function. In vitro imaging demonstrated a linear correlation between NIR-II fluorescence intensity and labeled cell numbers (R² = 0.973, p < 0.001), while MRI provided complementary anatomical context at higher cell densities. In an orthotopic glioma mouse model, longitudinal MRI and NIR-II imaging captured route-dependent differences in tumor-associated localization and whole-body biodistribution following intracerebroventricular and intravenous administration. Furthermore, organ-level NIR-II exposure showed a positive association with CD3⁺ T-cell density across organs (R² = 0.552, p < 0.001), supported by multi-organ pathological validation. Collectively, we establish a biocompatible dual-modality workflow that links intracranial anatomical localization with longitudinal whole-body biodistribution readouts for preclinical CAR-T tracking in solid tumor models.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147825929","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}