Cancer immunology, immunotherapy : CII最新文献

{"title":"Immunological impact of tumor-draining lymph node dissection on systemic Th1-like CD4⁺ T cells in patients with early-stage lung cancer.","authors":"Atsushi Kamigaichi, Hiroshi Kagamu, Yoshihiro Miyata, Takahiro Mimae, Norifumi Tsubokawa, Koichi Hirano, Morihito Okada","doi":"10.1007/s00262-026-04357-4","DOIUrl":"10.1007/s00262-026-04357-4","url":null,"abstract":"<p><strong>Introduction: </strong>Tumor-draining lymph nodes (LNs) are critical for initiating and maintaining antitumor immunity. However, systematic LN dissection (LND) remains the standard surgical procedure for lung cancer. This study aimed to investigate the immunological impact of tumor-draining LND on systemic T cell subsets.</p><p><strong>Methods: </strong>We prospectively analyzed perioperative peripheral blood and resected LN samples from patients with early-stage lung adenocarcinoma who underwent lobectomy with systematic LND (systematic LND group) or wedge resection without LND (LN-preserving group). Perioperative immune cell dynamics were comprehensively profiled using mass cytometry.</p><p><strong>Results: </strong>Unlike conventional CD4⁺ and CD8⁺ T cell subsets, Th7R (CXCR3^±CCR4^-CCR6⁺ CD62L^lowCD4⁺ T cell), a Th1-like CD4⁺ T cell cluster essential for antitumor immunity, consistently decreased in peripheral blood after tumor resection in both groups (p = 0.0016 and p = 0.0033). This decline was significantly milder in the LN-preserving group than in the systematic LND group (p = 0.0153). In LN analyses, Th7R percentages were significantly higher in hilar, interlobar, and peripheral LNs than in subcarinal and other mediastinal LNs (p = 0.0148). Th7R percentages in resected LNs strongly and negatively correlated with postoperative changes in peripheral blood (r = -0.857, p = 0.0137). Furthermore, greater declines in Th7R in peripheral blood were associated with postoperative oncological disease events.</p><p><strong>Conclusions: </strong>Preserving LNs contributes to maintaining systemic antitumor immunity after surgery for early-stage lung cancer. Hilar, interlobar, and peripheral LNs may serve as primary reservoirs and supply sources of Th7R. In early-stage disease, these findings suggest a potential immunological benefit of LN-preserving strategies.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13125411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794872","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":"AdvanTIG-206: a phase II, randomized study of ociperlimab plus tislelizumab and BAT1706 (bevacizumab biosimilar) versus tislelizumab and BAT1706 in first-line hepatocellular carcinoma.","authors":"Zhenggang Ren, Yao Huang, Yabing Guo, Ming-Mo Hou, Wei Wang, Ming Kuang, Chunyi Hao, Wentao Wang, Yanqiao Zhang, Tianqiang Song, Chaoliu Dai, Hsing-Tao Kuo, Zinan Bao, Yunxia Zuo, Lei Wang, Fuxiang Zhu, Jia Fan","doi":"10.1007/s00262-026-04399-8","DOIUrl":"10.1007/s00262-026-04399-8","url":null,"abstract":"<p><strong>Background: </strong>Patients with hepatocellular carcinoma (HCC) have an unmet need for new therapies that improve survival. This phase II trial investigated the efficacy and safety of ociperlimab and tislelizumab plus BAT1706 (a bevacizumab biosimilar) in patients with first-line HCC.</p><p><strong>Methods: </strong>In this phase II, multicenter, randomized, multi-arm, open-label trial, patients with advanced HCC received ociperlimab and tislelizumab plus BAT1706 (Arm A) or tislelizumab plus BAT1706 (Arm B). The primary objective was to evaluate efficacy using objective response rate (ORR) assessed by the investigator per RESIST v1.1 for Arms A and B.</p><p><strong>Results: </strong>94 patients were randomized to Arm A (N = 62) and Arm B (N = 32). Confirmed ORR (95% confidence interval) was 37.1% (25.2-50.3) for Arm A and 40.6% (23.7-59.4) for Arm B. In Arms A and B, respectively, 90.3% and 80.6% of patients experienced treatment-related treatment-emergent adverse events (TEAEs), 59.7% and 32.3% experienced Grade ≥ 3 treatment-related TEAEs and 22.6% and 9.7% experienced treatment-related TEAEs leading to treatment discontinuation. Immune-mediated adverse events were reported in 50.0% of patients in Arm A and 45.2% of patients in Arm B. Infusion-related reactions occurred in a single patient in Arm A.</p><p><strong>Conclusion: </strong>In patients with advanced HCC, tislelizumab plus BAT1706 demonstrated promising ORR, while adding ociperlimab was not associated with improved efficacy. The safety profile of ociperlimab and tislelizumab plus BAT1706 was tolerable and manageable, with no new safety signals identified.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT04948697 (September 20, 2021).</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13125556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794827","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":"Neutral sphingomyelinases restrict natural killer cells activity against lung cancer.","authors":"Riccardo Cinotti, Mannon Geindreau, Anna Bergqvist, Ying Yang, Andreas Lundqvist","doi":"10.1007/s00262-026-04393-0","DOIUrl":"https://doi.org/10.1007/s00262-026-04393-0","url":null,"abstract":"<p><p>High frequency and activity of tumor-infiltrating natural killer (NK) cell is associated with improved prognosis in several solid cancers including non-small cell lung cancer. However, multiple factors can suppress NK cell activity within the tumor microenvironment, resulting in impaired killing of tumor cells. For NK cells to engage and kill target cells, stabilization of lipid rafts is essential. Sphingomyelin is involved in lipid raft formation and is catabolized by sphingomyelinases. While inhibition of sphingomyelinases enhances NK cell-mediated killing of tumor cells, it is unknown how sphingomyelinases impact on the ability of NK cells to infiltrate solid tumors. Here we demonstrate that inhibition of sphingomyelinases results in increased activation and ability of NK cells to infiltrate lung adenocarcinoma. Overall, our findings support the use of sphingomyelinase inhibitors as enhancers of NK cell activation.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794911","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":"CD39/CD73-mediated immunosuppression and tumor aggressiveness in bladder cancer.","authors":"Frederico Furriel, Paula Laranjeira, Margarida Pereira, Sandra Silva, Isabel Silva, Guilherme Fontinha, Vítor Sousa, Célia Gomes, Belmiro Parada, Artur Paiva","doi":"10.1007/s00262-026-04400-4","DOIUrl":"https://doi.org/10.1007/s00262-026-04400-4","url":null,"abstract":"<p><p>Urothelial bladder cancer (BCa) is marked by high recurrence and mortality, and the efficacy of PD-1/PD-L1 immunotherapy remains limited because of immune evasion. The adenosinergic pathway (AP), mediated by ectonucleotidases CD39 and CD73, is a key immunosuppressive mechanism, but its role in BCa remains unclear. We conducted an integrated immunophenotypic analysis of peripheral blood (PB) and the tumor microenvironment (TME) from 39 patients with BCa and 14 healthy controls using multicolor flow cytometry and immunohistochemistry. High-risk (HR) patients exhibited systemic immunosuppression, characterized by an elevated neutrophil-to-lymphocyte ratio and increased circulating regulatory T cells (Tregs), along with reduced cytotoxic γδ T cells and diminished Th1/Tc1 functional subtypes. In the TME, we observed reduced CD8⁺ T cell infiltration accompanied by increased Tregs, and phenotypes characterized by poor immune infiltration in the tumor core predominated across the cohort. In both PB and the TME, CD39 and CD73 expression on T cells strongly correlated with an immunosuppressive environment, marked by increased M2-like macrophages and decreased effector T cells. Circulating double-positive T cells (CD4⁺CD39⁺CD73⁺ and CD8⁺CD39⁺CD73⁺) mirrored the intratumoral T-cell composition, suggesting their potential as non-invasive biomarkers. Elevated frequencies of circulating single-positive CD8⁺CD39⁺ and CD8⁺CD73⁺ T-cells were significantly associated with higher pathological grade and distinguished high-grade tumors with moderate accuracy (AUC > 0.70). This study demonstrates that BCa is characterized by extensive AP-linked immunosuppression, and that specific ectonucleotidase-expressing circulating T-cell subsets may serve as non-invasive biomarkers for assessing tumor infiltration and grade.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13103164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794852","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 and prioritisation of tumour antigen candidates from 79 glioblastoma transcriptomes.","authors":"Špela Kert, Jože Pižem, Sara Petrin, Matic Bošnjak, Miha Jerala, Alenka Matjašič, Andrej Zupan","doi":"10.1007/s00262-026-04390-3","DOIUrl":"https://doi.org/10.1007/s00262-026-04390-3","url":null,"abstract":"<p><p>Glioblastoma (GBM) is an aggressive brain tumour with limited responsiveness to current immunotherapeutic approaches, partly due to its low mutational burden and intra-tumour heterogeneity. A systematic understanding of the tumour antigen landscape is therefore essential for advancing tumour immunology and supporting rational development of immunotherapeutic strategies. In this study, we performed whole-transcriptome sequencing of RNA extracted from 79 formalin-fixed paraffin-embedded (FFPE) IDH-wildtype GBM samples to systematically identify and prioritise candidate tumour antigens derived from three sources: single-nucleotide variants (SNVs), overexpressed tumour-associated antigens (TAAs), and gene fusion events. Candidate peptides were evaluated using integrated computational criteria, including transcript expression, predicted antigen processing features, peptide-HLA binding affinity and stability. Across the cohort, mutation-derived tumor-specific antigens (TSAs) were largely private to individual samples, whereas TAAs constituted a larger and more recurrent candidate pool. Despite comparable predicted binding characteristics across antigen classes, recurrence patterns differed substantially, reflecting their distinct biological origins. Fusion-derived candidates were rare and sample-specific. Predicted peptide presentation was disproportionately associated with a limited subset of HLA class I alleles. Collectively, this study provides a systematically prioritized catalogue of transcriptionally expressed GBM antigen candidates and offers a comparative evaluation of mutation-, expression-, and fusion-derived antigen sources within a unified transcriptome-based framework.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794772","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":"KSR2 functions as a metabolic checkpoint for anti-PD-1 resistance by reprogramming glucose metabolism.","authors":"Yuli Ge, Qiong Zhou, Qiangqiang Zhang, Yanyan Hu, Rui Wang","doi":"10.1007/s00262-026-04394-z","DOIUrl":"https://doi.org/10.1007/s00262-026-04394-z","url":null,"abstract":"<p><p>Immune checkpoint blockade targeting the PD-1/PD-L1 axis has revolutionized cancer therapy, yet the frequent emergence of resistance limits its clinical efficacy. Elucidating the mechanisms underlying resistance and developing effective strategies remain critical challenges in tumor immunotherapy. This study identifies kinase suppressor of Ras 2 (KSR2) as a driver of resistance to anti-PD-1 therapy in lung cancer. Transcriptomic analysis of an anti-PD-1-resistant mouse model and public clinical datasets revealed upregulation of KSR2 in resistant tumors. In vivo functional studies demonstrated that KSR2 overexpression is sufficient to confer resistance, while its knockdown resensitizes tumors to PD-1 blockade. Mechanistically, KSR2 functions as a central metabolic checkpoint, driving profound glucose metabolic reprogramming in cancer cells by enhancing glucose uptake, potentiating the Warburg effect, promoting lactate accumulation, and disrupting the tricarboxylic acid cycle. This metabolic reprogramming was subsequently associated with an immunosuppressive tumor microenvironment, characterized by reduced infiltration and impaired function of CD8⁺ T cells, alongside an enrichment of regulatory T cells. These findings suggest that KSR2 plays a role in modulating immunotherapy response, indicating a potential link between tumor metabolism and immune evasion. KSR2 emerges as a candidate target for further exploration in overcoming anti-PD-1 resistance.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794870","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":"Repurposing public sarcoma multi-omics for neoantigen discovery.","authors":"Panagiotis Mantas, Karen A Krogfelt","doi":"10.1007/s00262-026-04395-y","DOIUrl":"https://doi.org/10.1007/s00262-026-04395-y","url":null,"abstract":"<p><strong>Background: </strong>Soft tissue sarcomas, particularly complex karyotype sarcomas (CKS), are characterized as \"immunologically cold\" malignancies driven by structural instability rather than a high tumor mutational burden (TMB). Public \"legacy\" cohorts are a useful resource to uncover immunotherapy biomarkers. This study used the whole-exome sequencing (WES) and RNA-sequencing of CKS patients, to overcome technical limitations and to identify and prioritize neoantigens.</p><p><strong>Methods: </strong>The systematic immunogenomic reanalysis was performed on a landmark cohort of CKS patients (Kim et al., 2018) with a custom bioinformatics workflow which was developed to uncover interpretable immunogenomic signals. This approach consisted of: (1) defining a quality-controlled \"callable territory\" and normalizing TMB metrics, respectively; (2) utilizing RNA-seq not only for expression filtering but as an orthogonal validation check for variant transcription and to distinguish functional amplifications from technical depth artifacts; and (3) applying a multi-modal epitope prediction pipeline to identify and prioritize high-affinity neoantigens derived from both somatic SNVs, indels and expressed gene fusions.</p><p><strong>Results: </strong>The reanalysis shows that standard genome-wide metrics frequently underestimated the immunogenic potential. Normalizing the TMB refined quantitative mutation burden estimates and improved interpretation of low-coverage samples without essentially changing the overall cohort classification. Furthermore, integration of transcriptomic data facilitated the recovery of actionable targets in \"low-TMB\" tumors. A subset of fusion-derived peptides demonstrated predicted binding affinities competitive with SNV-derived candidates.</p><p><strong>Conclusion: </strong>This study illustrates that technically constrained multi-omic datasets can be systematically re-analyzed to identify potential therapeutic targets. These data argue for looking beyond aggregate biomarkers; patient-specific, expressed neoepitopes may exist even in sarcomas typically described as immunologically \"cold\".</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794986","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":"Envafolimab combined with lenvatinib and albumin-bound paclitaxel in previously treated advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma: a prospective, phase II, multi-cohort trial.","authors":"Zhao Xiaoying, Feng Wanjing, Geng Qirong, Huang Mingzhu, Zhang Zhe, Chen Jinsi, Sheng Xuedan, Zhu Xiaodong, Guo Weijian","doi":"10.1007/s00262-026-04373-4","DOIUrl":"https://doi.org/10.1007/s00262-026-04373-4","url":null,"abstract":"<p><strong>Background: </strong>This single-center, open-label, exploratory trial aimed to investigate the efficacy and safety of envafolimab combined with lenvatinib and chemotherapy in previous treated advanced G/GEJ adenocarcinoma.</p><p><strong>Methods: </strong>Eligible patients with HER2-negative, microsatellite stable (MSS) advanced G/GEJ adenocarcinoma who had progressed after first-line treatment were enrolled in this phase II trial. Patients without previously receiving PD-1/PD-L1 inhibitors were enrolled in Group A, and those who progressed on the first-line PD-1 inhibitors were included in Group B. Patients in both groups received envafolimab (200 mg, subcutaneous injection (sc), days 1 and 15, Q4W) combined with lenvatinib and albumin-bound paclitaxel (100 mg/m², IV, days 1, 8 and 15, Q4W, up to 6 cycles) until disease progression, unacceptable toxicity, or refusal of continuation. The primary endpoint was objective response rate (ORR).</p><p><strong>Results: </strong>A total of 30 patients were included for safety and efficacy analysis. As of data cutoff (Sep 14, 2024), the median follow-up was 17.0 months (IQR: 8.0-18.8) in Group A. The ORR was 60.0%, and the DCR was 100.0%. The mPFS was 8.2 months (95% CI 6.1-10.4) with mOS of 14.8 months (95% CI 7.4-22.2). With a median follow-up of 9.0 months (IQR: 6.1-16.2) in Group B, the ORR was 46.7%, and the DCR was 100.0%. The mPFS was 5.9 months (95% CI 3.8-8.1), and the mOS was 11.5 months (95% CI 3.1-19.9). The overall incidence of adverse events (AEs) of any grade was 100%. While Group A showed numerically better outcomes than Group B, there was no statistically significant difference in PFS (P = 0.629) or OS (P = 0.873) between the two groups.</p><p><strong>Conclusions: </strong>Second-line envafolimab-based combination therapy demonstrated promising effects in previously treated advanced GC, particularly in those who have not previously received ICIs.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794764","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":"IL-18-armed oncolytic vaccinia virus remodels the suppressive microenvironment via macrophage and Treg modulation in lymphoma.","authors":"Hui Wu, Jiaqing Zhang, Li Xu, Yifan Xie, Lingli Pan, Xinyue Zhang, Yongming Xia, Fang Yang, Xiaozhen Kang, Xiangmin Tong, Shibing Wang","doi":"10.1007/s00262-026-04396-x","DOIUrl":"https://doi.org/10.1007/s00262-026-04396-x","url":null,"abstract":"<p><strong>Introduction: </strong>Lymphoma is a heterogeneous hematological malignancy with limited effective therapies. Oncolytic vaccinia virus (OVV) is a promising immunotherapy, but its monotherapeutic efficacy is suboptimal, showing weak antitumor activity in murine lymphoma models and inducing an immunosuppressive tumor microenvironment (TME) with more M2 macrophages and Tregs. This study aimed to improve OVV's efficacy and translational feasibility by reversing the immunosuppressive TME and enhancing OVV-mediated antitumor immunity.</p><p><strong>Methods: </strong>We first explored IL-18's effect on OVV-induced immunosuppressive TME, then engineered a recombinant OVV-hIL18 encoding human IL-18. We assessed its in vitro oncolytic activity, in vivo antitumor effect and safety in murine/humanized lymphoma models, and its TME-regulating mechanisms.</p><p><strong>Results: </strong>IL-18 reversed OVV-induced immunosuppression by promoting M1 polarization and reducing Tregs, boosting OVV-mediated immunity. OVV-hIL18 had enhanced in vitro oncolysis, significantly inhibited tumor growth, prolonged survival in animal models without overt toxicity, and increased CD4⁺/CD8⁺ T cell infiltration, effector cytokine production and relieved T cell exhaustion in TME.</p><p><strong>Conclusion: </strong>IL-18-armed OVV overcomes OVV monotherapy limitations and enhances antitumor efficacy, providing theoretical and experimental support for its development as a next-generation immunotherapy for lymphoma.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147794821","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":"Immunotherapy for pediatric solid tumors: overcoming biological barriers through rational multimodal combinations.","authors":"Mahsa Fatahichegeni, Mohammad Amin Ansarian, Mi Xiao, Wenjuan Gao, Ruiming Shi","doi":"10.1007/s00262-026-04384-1","DOIUrl":"10.1007/s00262-026-04384-1","url":null,"abstract":"<p><p>Pediatric solid tumors remain among the most treatment-refractory childhood malignancies, defined by biological features that have largely resisted the immunotherapeutic advances transforming adult oncology. Exceptionally low tumor mutational burden, sparse neoantigen landscapes, and profoundly immunosuppressive tumor microenvironments collectively undermine the T cell-dependent mechanisms on which most current immunotherapies depend. Yet the field is undergoing a meaningful shift. Anti-GD2 monoclonal antibodies have established a survival benchmark in high-risk neuroblastoma, and next-generation antibody-drug conjugates and bispecific T cell engagers targeting GD2, B7-H3, and GPC2 are extending the reach of antibody-based approaches across pediatric histologies. CAR T cell therapies have demonstrated clinical feasibility against multiple targets, with advanced engineering strategies, including cytokine armoring, bispecific constructs, and locoregional delivery, beginning to address fundamental barriers such as poor tumor infiltration, limited persistence, and antigen escape. Immune checkpoint inhibitors, while largely ineffective as monotherapy in unselected populations, induce durable responses in molecularly defined subsets such as mismatch repair-deficient and hypermutated tumors. Emerging platforms, including oncolytic virotherapy, NK cell engagers, and neoantigen vaccines, offer rational strategies to convert immunologically cold tumors into treatment-responsive phenotypes. Together, these advances point toward a future of combination immunotherapy tailored to the distinct immune biology of childhood cancers.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 5","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13083667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694732","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}