Cancer immunology, immunotherapy : CII最新文献

{"title":"Beyond radiation: immunological potentials of boron neutron capture therapy.","authors":"Muyasha Abulimiti, Yu Sugawara, Yinuo Li, Hideyuki Sakurai, Yoshitaka Matsumoto","doi":"10.1007/s00262-026-04424-w","DOIUrl":"10.1007/s00262-026-04424-w","url":null,"abstract":"<p><p>Boron neutron capture therapy (BNCT) is a targeted radiotherapeutic modality that employs boron-10 (¹⁰B) to capture thermal neutrons, thereby releasing high-linear energy transfer α-particles and lithium ions that selectively eradicate tumor cells while sparing the surrounding normal tissues. Immune checkpoint inhibitors (ICIs), including inhibitors of PD-1/PD-L1 and CTLA-4, enhance antitumor immunity by alleviating immunosuppression within the tumor microenvironment. As immunotherapy continues to expand across multiple tumor types and becomes integral to systemic cancer treatment, attention has increasingly focused on combining systemic immunomodulation with localized therapies. BNCT functions primarily as a local therapeutic approach, whereas ICIs elicit systemic immune activation. Whether the two modalities can produce synergistic therapeutic effects remains an important question.In this narrative review, we summarize current mechanistic insights, preclinical and clinical developments, and ongoing challenges associated with the combination of BNCT and ICIs, highlighting the potential of this strategy to achieve durable, synergistic antitumor responses.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148230481","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 to: Bevacizumab reduces PD-L1 Not PD-1 inhibitor-associated pneumonitis in non-small cell lung cancer patients.","authors":"Lingling Wang, Yasi Xu, Yanyan Zhao, Bing Xia, Lucheng Zhu","doi":"10.1007/s00262-026-04445-5","DOIUrl":"10.1007/s00262-026-04445-5","url":null,"abstract":"","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"75 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13253931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148221478","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":"Low-dose IL-2 therapy for immune-related adverse events via Tfh/Treg balance modulation: a prospective cohort and murine model study.","authors":"Yifan Wang, Zhening Zhang, Yufei Li, Yongjing Cheng, Min Wang, Yudong Liu, Hao Li, Zhi Peng, Jing He","doi":"10.1007/s00262-026-04452-6","DOIUrl":"10.1007/s00262-026-04452-6","url":null,"abstract":"<p><strong>Background: </strong>Immune-related adverse events (irAEs) are associated with anti-PD-1/PD-L1 therapy in gastrointestinal cancers. Altered phenotypes and frequencies of T cell subsets play a critical role in irAEs. This study characterized the Tfh/Treg balance in irAEs patients and assessed the efficacy of LDIL-2 therapy in mouse models.</p><p><strong>Methods: </strong>A prospective study evaluating the immunological characteristics of 26 gastrointestinal cancer patients through both cellular and transcriptomic analyses before and after anti-PD-1/PD-L1 therapy was performed. Patients were categorized into two groups: the AE group (patients who developed irAEs during the follow-up period) and the NAE group (patients who did not). Meanwhile, MRL/MpJ-Fas^lpr mice, a lupus mouse model, and tumor-bearing C57BL/6 J mice were used to evaluate the efficacy of LDIL-2 in treating anti-PD-L1 induced irAEs and its impact on antitumor effectiveness.</p><p><strong>Results: </strong>Our study discovered that in AE patients, Tfh-related genes were significantly upregulated during the early stages of anti-PD-1/PD-L1 therapy (IL-21: p < 0.01; PDCD1: p < 0.05), whereas the upregulation of Treg-related genes was less pronounced compared to Tfh-related genes. This distinction was not observed in NAE patients. Flow cytometry results further confirmed a substantial increase in the Tfh/Treg ratio in AE patients during the early stages of therapy (p < 0.001), a phenomenon absent in NAE patients. In MRL/MpJ-Fas^lpr mice, anti-PD-L1 therapy induced a shift in the Tfh/Treg ratio, along with severe organ inflammatory lesions and elevated anti-dsDNA antibody levels. In contrast, LDIL-2 treated mice maintained a balanced Tfh/Treg ratio, exhibiting significantly fewer organ inflammatory lesions and reduced anti-dsDNA production. Furthermore, in tumor-bearing mice, LDIL-2 did not impair the antitumor efficacy of anti-PD-L1 therapy.</p><p><strong>Conclusions: </strong>Our study underscores the importance of Tfh/Treg balance in the development of irAEs and demonstrates the potential of LDIL-2 as a therapeutic option for irAEs, providing a promising alternative to traditional immunosuppressive therapies for managing irAEs.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148207543","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":"Optimizing the clinical assessment of pseudoprogression in patients with solid tumors treated with checkpoint inhibitors: a systematic literature review and meta-analysis of associated features.","authors":"Georgios Fountoukidis, Elisabet Tina, Anna Göthlin-Eremo, Gustav Ullenhag, Antonios Valachis","doi":"10.1007/s00262-026-04433-9","DOIUrl":"10.1007/s00262-026-04433-9","url":null,"abstract":"<p><strong>Background: </strong>Pseudoprogression is an atypical response pattern observed during treatment with immune checkpoint inhibitors (CPIs) that can complicate clinical decision-making. It is characterized by initial radiologic progression followed by subsequent tumor regression or stabilization, with confirmation requiring repeat imaging. We aimed to characterize the clinical and imaging features of confirmed pseudoprogression in solid tumors treated with CPIs using pooled study data.</p><p><strong>Methods: </strong>We systematically searched MEDLINE, Embase, and Web of Science through December 2025. Prospective and retrospective cohort studies and randomized trials reporting confirmed pseudoprogression during CPI therapy were eligible. Two independent reviewers performed study selection and data extraction using predefined criteria. Study quality was assessed using the Joanna Briggs Institute checklist. Pooled analyses were conducted with RevMan and Stata. Outcomes included time to initial radiologic progression, magnitude of tumor burden increase, occurrence of new lesions, changes in nontarget lesions, and subsequent objective response.</p><p><strong>Results: </strong>Thirteen retrospective studies were included; most applied iRECIST criteria. The pooled median time to initial progression was 2.52 months (95% CI, 1.54-3.51). Mean tumor burden increase was 33.0% (95% CI, 22.7-43.3), and new lesions occurred in 35.3% of cases. Tumor burden increases > 100% were rare (3.9%). Despite initial progression, 41.8% subsequently achieved partial response and 6.4% complete response without therapy change. Median time to best response was 2.79 months (95% CI, 0.62-7.20).</p><p><strong>Conclusions: </strong>Pseudoprogression typically occurs early during CPI therapy and is associated with modest tumor growth. Marked tumor increases are uncommon and may help distinguish true progression. Careful clinical and radiologic assessment remains essential.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13264642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201939","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-cold NSCLC tumors harbor tumor-associated macrophages with elevated expression of immunoglobulin genes.","authors":"Markus Haug, Henrik Sahlin Pettersen, Magne Børset, Arne Kildahl-Andersen, Sissel Gyrid Freim Wahl, Arnar Flatberg, Anders Tøndell","doi":"10.1007/s00262-026-04446-4","DOIUrl":"10.1007/s00262-026-04446-4","url":null,"abstract":"<p><p>In the non-small cell lung cancer (NSCLC) tumor microenvironment (TME), tumor cells mediate inhibitory signals to key immune cells, promoting an immunosuppressive environment that facilitates tumor immune evasion. CD8 + cytotoxic T lymphocytes are central mediators of antitumor immunity, and tumors can be classified by immunohistochemistry (IHC) as immune-hot or immune-cold based on the abundance of tumor-infiltrating lymphocytes (TILs). Although cancer immunotherapy can boost lymphocyte functions and improve progression-free survival in patients with advanced NSCLC, only a minority of patients experience a durable clinical benefit. Tumor-associated macrophages (TAMs) are key immunoregulatory cells in the NSCLC microenvironment and capable of generating potent immunosuppressive signals. However, their functional roles in immune-hot versus immune-cold tumors remain poorly understood. In this study, we compared the transcriptional programs of TAMs from NSCLC patients with immune-hot or immune-cold tumors. We classified 11 surgically resected NSCLC tumors as immune‑hot or immune‑cold based on quantitative immunohistochemistry of CD4⁺ and CD8⁺ tumor‑infiltrating lymphocytes. TAMs were isolated from tumor and adjacent healthy tissue by fluorescence-activated cell sorting (FACS), followed by bulk RNA sequencing and differential gene expression analysis. TAMs from immune‑cold tumors exhibited a striking upregulation of genes involved in immunoglobulin-mediated immune responses. Additionally, these TAMs demonstrated increased expression of genes involved in extracellular matrix organization, including matrix metalloproteinases and collagen‑associated genes, suggesting enhanced matrix remodeling activity. These findings highlight TAMs' potential contribution to immunosuppression, stromal remodeling, and impaired lymphocyte infiltration. The TAM-mediated pathways identified here may represent actionable targets for future immunotherapeutic strategies aimed at reshaping the tumor microenvironment.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148195331","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":"Explainable AI reveals squamous histology and U-shaped PD-L1 patterns as primary subgroup predictors of neoadjuvant and perioperative immunotherapy benefit in NSCLC: a machine learning analysis.","authors":"Fangfang Shen, Zheqing Zhu, Junge Liu, Feng Li","doi":"10.1007/s00262-026-04450-8","DOIUrl":"10.1007/s00262-026-04450-8","url":null,"abstract":"<p><strong>Background: </strong>The introduction of neoadjuvant and perioperative immunotherapy has broadened treatment options for resectable non-small cell lung cancer (NSCLC). However, clinical benefit varies across subpopulations, and standard linear models cannot fully capture the complex feature interactions and trial-level differences found in aggregate data.</p><p><strong>Methods: </strong>We applied an integrated framework combining multilevel meta-regression with an inverse-variance weighted eXtreme Gradient Boosting (XGBoost) algorithm. SHapley Additive exPlanations (SHAP) were used to interpret the model and identify efficacy variance drivers across seven randomized controlled trials.</p><p><strong>Results: </strong>Multilevel meta-regression demonstrated that event-free survival (EFS) benefit correlated positively with PD-L1 expression, peaking in the <math><mo>≥</mo></math> 50% subgroup (adjusted HR = 0.44, 95% CI: 0.33--0.57). XGBoost-SHAP analysis revealed trial-level variance as the dominant driver of heterogeneity. Among subgroup-level clinical covariates, a non-linear U-shaped PD-L1 predictive pattern (<1% and <math><mo>≥</mo></math> 50%), squamous cell carcinoma (SCC) histology (HR = 0.53, 95% CI: 0.43--0.65), and smoking history emerged as primary predictors. Synthesizing these signatures into a hypothesis-generating subgroup stratification framework indicated that SCC and PD-L1-negative (<1%) non-squamous cohorts benefit from continuous perioperative blockade. Conversely, exploratory analyses suggested that PD-L1-positive ( <math><mo>≥</mo></math> 1%) non-squamous tumors achieved maximal observed benefit from exclusively neoadjuvant regimens (HR = 0.50).</p><p><strong>Conclusions: </strong>Our results suggest that for PD-L1-positive non-squamous cases, the added benefit of extended adjuvant therapy may be limited. However, given our reliance on aggregate data and trial-level imbalances, these findings remain hypothesis-generating and should not alter current clinical practice. Rather, they offer an exploratory framework to inform patient selection for future de-escalation trials.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13462006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148177243","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":"Pan-cancer single-cell and spatial transcriptomics analyses delineate response-associated heterogeneity and therapeutic targets of tumor-infiltrating B cells following immune checkpoint blockade.","authors":"Jialing Fang, Hangyu Liu, Jun Lei, Yongshun Chen, Jingjing Wang","doi":"10.1007/s00262-026-04449-1","DOIUrl":"10.1007/s00262-026-04449-1","url":null,"abstract":"<p><p>Tumor-infiltrating B cells (TIBs) are emerging as central regulators of anti-tumor immunity, but their biological functions, spatial niches, and cross talk with tumor-infiltrating lymphocytes vary widely across cancer types, particularly with regard to cancer immunotherapies. Yet a pan-cancer atlas linking their transcriptional profile to the immune checkpoint blockade (ICB) response has been missing. Here, we presented the pan-cancer ICB response B cell atlas, constructed from 688 single-cell transcriptomes (24 cancer types, 241,645 cells). Twenty-four B cell subsets were identified, and their proportion dynamics and transcriptomic features across cancers were revealed. B cell subsets proportion-based NMF analyses identified 5 TIME subtypes in which TIME-Plasma and TIME-Memory showing repressed apoptosis, higher antigen presentation, and enrichment in responders were correlated with better survival in several cancers. Pseudo-time trajectories delineated two conserved differentiation pathways that branch at the memory B cell node and showed distinct correlations with B cell apoptosis and ICB response. Pan-cancer spatial deconvolution showed that several responder-derived B cell subsets including plasma cells, memory B cells, and activated B cells were more co-occurred compared to non-responder-derived B cell subsets. Utilizing pan-cancer TCGA datasets, the clinical heterogeneity of B cell subsets from distinct response groups was revealed. We constructed a pan-cancer ICB response Geneformer model and in silico perturbed all genes. Thirteen candidate genes, which were significantly correlated with the B cell ICB response state transition, were identified. Overall, our study illuminates the heterogeneity of TIBs and improves our understanding of cancer-specific B cell subsets within the context of tumor immunotherapies.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13461987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148166847","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":"Enhanced PD-L1 targeting boosts the cytotoxic activity of FOLR1- CAR NK92 cells against ovarian cancer.","authors":"Xuena Chen, Jie Huang, Ge Diao, Min Tian, Yu Yang, Dan Liu, Yunhe Ma, Jian Han, Jianxin Guo","doi":"10.1007/s00262-026-04443-7","DOIUrl":"10.1007/s00262-026-04443-7","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR)-T cells have achieved remarkable success against hematologic malignancies; however, their application is associated with risks such as cytokine release syndrome (CRS) and neurotoxicity. In contrast, CAR-NK cells not only avoid these toxicities but also retain the natural cytotoxic activity of NK cells, demonstrating great potential for cancer immunotherapy.Our previous study demonstrated the potent efficacy of folate receptor alpha (FOLR1)-targeted CAR-NK92 cells against ovarian cancer (OC). Nevertheless, the application of CAR-NK therapy in solid tumors, including OC, still faces challenges such as tumor antigen heterogeneity and the immunosuppressive tumor microenvironment (ITME). A key mediator of ITME is programmed death-ligand 1 (PD-L1), which not only correlates with poor prognosis in OC but also drives T cell exhaustion via the PD-1/PD-L1 axis. Moreover, its inducible upregulation under NK cell-based therapy supports PD-L1 as a viable therapeutic target in OC.To enhance the therapeutic potential of CAR technology for OC, we engineered two novel third-generation bispecific CAR-NK92 cells based on our prior FOLR1-CAR design. These constructs-Tandem PD-L1/FOLR1-CAR (Tan-CAR1) NK92 and Tandem FOLR1/PD-L1-CAR (Tan-CAR2) NK92-were designed to simultaneously target FOLR1 and PD-L1. Notably, we confirmed that PD-L1 expression was significantly upregulated in the co-culture supernatant of effector and target cells. In vitro, Tan-CAR2 NK92 cells exhibited markedly superior cytotoxicity against FOLR1^highPD-L1^low OC cells and enhanced degranulation compared with FOLR1-CAR NK92 cells. In xenograft mouse models, Tan-CAR2 NK92 cells showed effective tumor infiltration and induced significantly greater tumor regression than both FOLR1-CAR NK92 and PD-L1-CAR NK92 groups. In conclusion, the tandem bispecific CAR-NK92 cells developed in this study represent a meaningful advance in immunotherapy. Their dual mechanism-broader antigen recognition and enhanced immune infiltration-effectively addresses two major therapeutic barriers in OC, offering a promising strategy for treating refractory cases.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13462002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148166742","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":"Integrated immunophenotypic and ProMisE molecular profiling as predictors of immune checkpoint inhibitor response in recurrent endometrial cancer.","authors":"Komei Katayama, Nobuhisa Yoshikawa, Wenting Liu, Kae Nakamura, Satomi Hattori, Mei Kubokawa, Shohei Iyoshi, Kosuke Yoshida, Masato Yoshihara, Yukari Nagao, Satoshi Tamauchi, Akira Yokoi, Kaoru Niimi, Yusuke Shimizu, Yosuke Kawai, Fumi Utsumi, Eri Watanabe, Shiro Suzuki, Kiyosumi Shibata, Hiroaki Kajiyama","doi":"10.1007/s00262-026-04414-y","DOIUrl":"10.1007/s00262-026-04414-y","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) are an important treatment option for recurrent endometrial cancer (EC); however, responses vary widely. Although the ProMisE molecular classification provides prognostic and predictive insights, it does not fully explain the heterogeneity of ICI outcomes. Further characterization of the tumor immune microenvironment (TIME) is required to refine biomarker development.</p><p><strong>Methods: </strong>We retrospectively analyzed 72 patients with recurrent EC treated with ICIs. Immune markers, including CD8, CD68, CD163, CD47, CD276, PD-L1, and HLA class I, were quantified using digital pathology. Associations between immune markers, ICI response, and progression-free survival (PFS) were evaluated overall and within ProMisE molecular subtypes. In an exploratory supplementary analysis, Foxp3 immunostaining was performed in 51 cases with additional FFPE material available.</p><p><strong>Results: </strong>Responders exhibited a more immunologically active TIME, characterized by increased CD8⁺ T-cell infiltration in the central tumor (CT), whereas non-responders showed enriched CD68⁺ tumor-associated macrophages at the invasive margin (IM) and higher CD47 expression. Distinct immune landscapes were observed across ProMisE subtypes. Mismatch repair-deficient (MMRd) tumors demonstrated higher intratumoral CD8+ infiltration, whereas p53-abnormal (p53abn) tumors showed a more immunosuppressive profile, including elevated CD163+ macrophage density and CD47 expression. Subtype-specific analyses revealed that PFS was associated with different immune determinants, including CD8+ T cell infiltration in MMRd, CD47 expression level in no specific molecular profile (NSMP), and CD68.IM in p53abn. In the Forkhead box P3 (Foxp3) subset, the CD8/Foxp3 ratio showed a stronger association with ICI response and PFS than Foxp3 alone.</p><p><strong>Conclusions: </strong>Tumor immune phenotypes provide clinically relevant information complementary to ProMisE classification. Rather than indicating a single universal determinant, our results support a model in which cytotoxic T-cell infiltration and immunosuppressive pathways jointly shape ICI outcome in recurrent EC. Integrating ProMisE classification with immunological profiling may improve patient stratification of ICI benefits.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13442805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148146066","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":"Preclinical evaluation of rBCG-h12: an engineered Bacillus Calmette-Guérin with an enhanced activity against bladder and pancreatic cancers.","authors":"Chang-Ching Yeh, Chi-Shuan Fan, Li-Li Chen, Kee Voon Chua, Chih-Hao Hsu, Chia-Chi Chen, Zhao-Lin Tan, Pei-Chu Tsai, Yung-Deng Song, Yong-Seng Low, Shiu-Ju Yang, Yih-Yuan Chen, Yi-Xiu Lin, Chia-Ming Wu, Horng-Yunn Dou, Tze-Sing Huang","doi":"10.1007/s00262-026-04441-9","DOIUrl":"10.1007/s00262-026-04441-9","url":null,"abstract":"<p><strong>Background: </strong>Intravesical Bacillus Calmette-Guérin (BCG) therapy has been the standard treatment for preventing recurrence of non-muscle-invasive bladder cancer (NMIBC) for over four decades. Although maintenance BCG therapy improves recurrence-free survival in intermediate- and high-risk NMIBC patients, its long treatment duration, toxicity, and limited efficacy - particularly in carcinoma in situ -necessitate the development of improved therapeutic alternatives. rBCG-h12 is a recombinant BCG strain engineered to enhance immunogenicity. This study evaluated its ability to augment macrophage activation and antitumor responses.</p><p><strong>Methods: </strong>The safety of intravesical rBCG-h12 was evaluated in NOD/SCID and C57BL/6 mice through four weekly instillations. Body weight, survival, urine hematuria, and organ histopathology were monitored. Antitumor efficacy was tested using an orthotopic NMIBC transplant model. Immune microenvironment changes were analyzed by detecting macrophage and T cell markers. The systemic antitumor potential of rBCG-h12 was further evaluated via intramuscular injection in pancreatic cancer transplant and K-Ras^G12D mouse models.</p><p><strong>Results: </strong>Intravesical rBCG-h12 was well tolerated, with no observed mortality, weight loss, hematuria, or organ pathology. Compared with conventional BCG, rBCG-h12 more effectively suppressed bladder tumor growth, prolonged survival, and mitigated cachexia. Mechanistically, rBCG-h12 decreased CD206⁺ M2-macrophages while increasing CD4⁺TNF-α⁺ effector T cells and CD8⁺TNF-α⁺ cytotoxic T cells. In pancreatic cancer models, a single intramuscular injection of rBCG-h12 markedly reduced desmoplasia, suppressed tumor growth, and extended survival without inducing pathological lesion or granuloma formation in liver, lungs, and spleen.</p><p><strong>Conclusions: </strong>rBCG-h12 exhibited superior antitumor efficacy and safety compared with BCG. By suppressing M2-macrophages and promoting Th1 immune activation, rBCG-h12 shows promise as a next-generation BCG-based immunotherapy for both bladder and pancreatic cancers.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13442775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148140654","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}