Cancer immunology, immunotherapy : CII最新文献

{"title":"The microbiota-lymphocyte protective axis (MLPA): a novel paradigm for overcoming radiation-induced lymphopenia (RIL) and potentiating the efficacy of tumor immuno-combination therapy.","authors":"Yilin Chen, Shuaixuan Chen, Hang Zhang, Binbin Song, Yufen Xu","doi":"10.1007/s00262-026-04442-8","DOIUrl":"10.1007/s00262-026-04442-8","url":null,"abstract":"<p><p>Combination therapy involving radiotherapy and immune checkpoint inhibitors has become a cornerstone of modern oncology; however, its therapeutic efficacy is frequently compromised by radiation-induced lymphopenia, a phenomenon traditionally viewed as an unavoidable physical consequence of radiation exposure. Accumulating evidence suggests that RIL also reflects broader host-dependent biological dysregulation, extending beyond direct lymphocyte depletion. In this review, we introduce the microbiota-lymphocyte protective axis as a conceptual and integrative framework to recontextualize RIL as a biologically modulated state influenced by the gut microenvironment. We synthesize current mechanistic and clinical evidence indicating that microbial-derived signals may shape immune competence during radiotherapy by influencing hematopoietic lineage commitment within the bone marrow, cellular stress tolerance mechanisms such as DNA damage responses and mitochondrial quality control, as well as systemic neuroendocrine stress pathways. This framework supports a shift toward a dual-modulatory strategy that integrates lymphocyte-sparing radiotherapy approaches (e.g., stereotactic body radiotherapy) with microbiota-targeted interventions (e.g., postbiotics). While further validation is required, the MLPA model provides a biologically grounded perspective that may help refine personalized radio-immunotherapy strategies.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148348531","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":"Timing of immune checkpoint inhibitors infusion and prognosis in recurrent/metastatic nasopharyngeal carcinoma: a single-center, retrospective study.","authors":"Lin Zhang, Xia Gan, Zhengzheng Yu, Wenji Xie, Xiaowen Sun, Yue Li, Jianing Fang, Yating Liu, Zhongjie Liu, Yaning Tang, Can Zhou, Zhuolong Xie, Shuyu Ouyang, Jing Zhang, Jingyu Wang, Hua Li, Feng Liu, Pan Chen, Yanxian Li, Hui Wang, Huai Liu","doi":"10.1007/s00262-026-04472-2","DOIUrl":"10.1007/s00262-026-04472-2","url":null,"abstract":"<p><strong>Background: </strong>The timing of immunotherapy administration has been linked to variations in clinical outcome across multiple cancers, but its effect on clinical outcome in nasopharyngeal carcinoma (NPC) remains unstudied.</p><p><strong>Methods: </strong>In this single-center retrospective cohort study, patients with recurrent/metastatic (R/M) NPC who received first-line anti-PD-1-based immunochemotherapy (June 2019-December 2024) were included. The primary endpoint was progression-free survival (PFS), and overall survival (OS) was the secondary endpoint. Data regarding the time of day of administration (ToDA) during the initial four cycles were collected for each patient. Survival was estimated by the Kaplan-Meier method and compared with log-rank tests. Multivariable Cox models were adjusted for prespecified covariates. Propensity score matching (PSM) was performed between patients from different ToDA groups. The ToDA cutoff was derived from the data without a prespecified hypothesis, using a data-driven approach.</p><p><strong>Results: </strong>Among the 334 screened patients, 312 met the eligibility criteria. The median follow-up was 24.9 months. The median PFS was 25.0 months, and the mOS was not reached. A data-driven optimal ToDA cutoff of 12:00 was identified. Patients who received immunotherapy after 12:00 had significantly longer PFS (31.2 vs. 18.3 months, p = 0.006) and OS (both not reached, p = 0.011). After PSM at a 1:2 ratio, PFS (36.1 vs. 18.3 months, p = 0.003) and OS (both not reached, p = 0.018) were still significantly improved in patients who received immunotherapy after 12:00. Multivariate analysis demonstrated that a ToDA after 12:00 was independently correlated with improved PFS (HR=0.63; 95% CI: 0.43-0.92; p = 0.017) and OS (HR=0.48; 95% CI: 0.27-0.84; p = 0.010).</p><p><strong>Conclusions: </strong>These hypothesis-generating findings suggest that, in R/M NPC patients treated with first-line immunochemotherapy, afternoon administration during the initial four cycles may be associated with improved PFS and OS. However, because the ToDA threshold was selected post hoc, the results should be interpreted with caution. Randomized clinical trials are warranted to validate these findings.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148348584","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":"CD68⁺ tumor-associated macrophages exhibit prognostic value in surgically resected small cell lung cancer: a retrospective cohort study of 614 patients.","authors":"Ruijie Ma, Hengjia Tu, Xingwu Wang, Peng Wu, Li Liu, Xuanyu Gu, Dongyu Li, Dexin Shang, Guochao Zhang, Chaoqi Zhang, Nan Sun, Jie He","doi":"10.1007/s00262-026-04417-9","DOIUrl":"https://doi.org/10.1007/s00262-026-04417-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment (TME) in small cell lung cancer (SCLC), yet the clinicopathological and prognostic relevance of CD68&lt;sup&gt;+&lt;/sup&gt; TAM infiltration in surgically resected SCLC remains insufficiently defined. We aimed to delineate the clinical significance of CD68&lt;sup&gt;+&lt;/sup&gt; cell density in surgically resected SCLC and develop an immune-integrated prognostic nomogram.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We retrospectively enrolled 614 patients with surgically resected SCLC from January 2000 to December 2022. CD68&lt;sup&gt;+&lt;/sup&gt; cell density and ASCL1/NeuroD1/POU2F3/YAP1 expression were assessed by immunohistochemistry. Cox regression identified independent prognostic factors, and nomograms were built and validated. Bulk transcriptomic analyses and immune deconvolution were performed to interpret CD68-associated biological programs. IHC staining for CD163, CD3, and CD8 was performed on a subset of 83 cases to validate computational findings at the tissue level.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In surgically resected SCLC samples, the median CD68&lt;sup&gt;+&lt;/sup&gt; cell density was 922.4/mm&lt;sup&gt;2&lt;/sup&gt;. CD68-high tumors showed higher proportions of NeuroD1 high expression, POU2F3 positivity, and YAP1 positivity (all p &lt; 0.05). Clinically, CD68-high status correlated with earlier T/N stage and fewer adverse invasion features (p &lt; 0.05). CD68-high infiltration was independently associated with improved overall survival (p &lt; 0.01) and disease-free survival (p &lt; 0.05); stratified Kaplan-Meier analyses confirmed that this prognostic benefit persisted within clinically homogeneous T-stage, N-stage, and TNM-stage subgroups (10 of 12 analyses, p &lt; 0.05). Nomograms incorporating CD68&lt;sup&gt;+&lt;/sup&gt; density and clinicopathological factors demonstrated favorable discrimination and calibration. Transcriptomic profiling and GSEA indicated that CD68-high SCLC were enriched for myeloid/chemokine signaling, antigen presentation, and T-cell-related pathways. Immune deconvolution supported higher monocytic lineage signals and elevated MHC components in CD68-high tumors, with correlation patterns consistent with M1-like macrophage signatures. IHC validation of CD163, CD3, and CD8 on 83 cases confirmed globally enhanced immune infiltration in CD68-high tumors, although the unchanged CD68/CD163 ratio indicated a proportional increase across macrophage subsets rather than a selective M1 shift.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;High CD68+ macrophage infiltration is an independent favorable prognostic factor in surgically resected SCLC. Transcriptomic and deconvolution analyses suggest that the CD68-defined immune heterogeneity is consistent with M1-like macrophage enrichment, although this inference is based on computational deconvolution. Preliminary IHC validation with CD163, CD3, and CD8 on a subset of 83 cases confirmed globally enhanced immune infiltration in CD68-high tumors. A CD68-","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148348528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory B-cell states in NSCLC immunotherapy resistance: mechanisms, spatial context and translational implications.","authors":"Xin Wang, Xi Li, Jing Zhou, Kai Yang, Rong Hu, Bin Pan","doi":"10.1007/s00262-026-04474-0","DOIUrl":"10.1007/s00262-026-04474-0","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors (ICIs) have improved clinical outcomes, durable benefit is limited by primary and acquired resistance arising from dynamic interactions between tumour cells and the tumour microenvironment. While current models remain largely T cell-centred, accumulating evidence indicates that B-cell states also shape therapeutic response. Here, we propose that regulatory B cells (Bregs) in NSCLC are best understood not as a fixed lineage, but as inducible Breg-associated states that may amplify immunotherapy resistance. We discuss how these states arise under tumour-driven conditions and are further shaped by spatial context, particularly within tertiary lymphoid structures (TLSs) and related immune niches. We further examine how Breg-associated states restrain antitumour immunity and interact with other immunosuppressive populations. This perspective reframes resistance beyond T cell-centric models and supports the development of biomarker-guided, functionally selective, and spatially informed therapeutic strategies.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148341886","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":"Efficacy and safety of anti-PD-1-based therapies in advanced melanoma across acral and mucosal subtypes: a nationwide retrospective cohort study.","authors":"Yuan Qiao, Xiao Fu, Iltaf Hussain, Weihong Ge, Wei Yang, Renbin Jiang, Xiaoyan Dai, Haisheng Chen, Jinyi Zhao, Meng Tang, Fei Mu, Hao Wang, Qiuhui Wu, Xing Xia, Yunnan Zhang, Suzhi Ji, Ying Xu, Xinrui Cao, Jiexin Wang, Le Gao, Jingwen Wang, Yu Yao, Yu Fang","doi":"10.1007/s00262-026-04460-6","DOIUrl":"10.1007/s00262-026-04460-6","url":null,"abstract":"<p><strong>Background: </strong>Acral melanoma (AM) and mucosal melanoma (MM) respond poorly to anti-PD-1 monotherapy. Therefore, there is an urgent need to explore safe and effective anti-PD-1-based combined therapies.</p><p><strong>Methods: </strong>A nationwide real-world cohort study consecutively included patients with advanced melanoma treated with anti-PD-1 in China between July 1, 2018, and June 30, 2023. The Research Electronic Data Capture (REDCap) system was used across all centers. The primary endpoints were progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs), with a secondary endpoints of objective response rate (ORR). Multivariable Cox and logistic regression models were conducted to compare the efficacy and safety of different anti-PD-1-based combination therapies with anti-PD-1 monotherapy. Stratified analyses were performed to evaluate the effect of therapies in cutaneous, acral, mucosal, and unknown primary subtypes.</p><p><strong>Results: </strong>A total of 431 advanced melanoma patients comprising 22% cutaneous, 39% acral, 32% mucosal, and 7% unknown primary subtypes were included. Multivariable Cox analysis indicated that compared with anti-PD-1 monotherapy, anti-PD-1 + anti-VEGF + chemotherapy (HR, 0.4 [0.2, 0.7], P = 0.005) and anti-PD-1 + anti-VEGF therapy (HR, 0.4 [0.2, 0.9], P = 0.018) showed significant PFS benefit in AM and MM, respectively. Notably, anti-PD-1 + IFN-α1b showed a nonsignificantly longer PFS and OS in AM. A multivariate logistic regression model found that anti-PD-1-based combination therapies were significantly associated with grade 1-2 irAEs, while only anti-PD-1 + IFN-α1b + anti-VEGF therapy was significantly associated with high risk of grade 3-5 irAEs (OR, 4.4 [1.3-14.7], p = 0.017), without a significant survival benefit.</p><p><strong>Conclusions: </strong>Our results provide evidence for anti-PD-1 + anti-VEGF + chemotherapy and anti-PD-1 + IFN-α1b in AM and anti-PD-1 + anti-VEGF therapy in MM, as the long-term benefit and acceptable toxicity. However, for the patients who received anti-PD-1 + IFN-α1b + anti-VEGF, cautionary notes and awareness of drug safety should be raised, as the triple therapy with multiple mechanisms may increase the potential risk of toxicity.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148303945","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":"Phase II study of 1st-line durvalumab and platinum-etoposide in advanced large-cell neuroendocrine lung carcinoma (aLCNEC).","authors":"Elizabeth Dudnik, Hovav Nechushtan, Ofer Rotem, Ekaterina Hanovich, Mira Wollner, Tatiana Boikaner, Niel Fridman, Jonathan Ofer, Merav A Ben-David, Daniel Reinhorn","doi":"10.1007/s00262-026-04464-2","DOIUrl":"10.1007/s00262-026-04464-2","url":null,"abstract":"<p><strong>Background: </strong>LCNEC is a rare high-grade neuroendocrine malignancy with poor prognosis and limited evidence to guide systemic therapy.</p><p><strong>Methods: </strong>Prospective, single-arm phase II study of 1st-line durvalumab 1500 mg + cisplatin or carboplatin and etoposide (EP) q3 weeks for 4 cycles, followed by durvalumab 1500 mg q4 weeks, in aLCNEC. The primary endpoint was 12-month PFS (RECIST v1.1, radiologist-assessed); secondary endpoints were ORR, OS, and safety. Sample size followed a single-stage Fleming design (one-sided α = 0.10, power 80%) testing a 12-month PFS rate ≤ 5% (H0) vs ≥ 18% (H1). The study closed early due to slow accrual after twelve of twenty-two planned patients were enrolled.</p><p><strong>Results: </strong>Twelve patients were treated (median age 68y; 66.7% male; 91.7% smokers; 91.7% stage IVB). After median follow-up of 12.8 months (95% CI 8.5-21.3), 92% had progressed and 75% had died. Median PFS was 4.4 months (95% CI 3.1-12.9); 12-month PFS was 25.0% (95% CI 6.0-50.5), exceeding the ≤ 5% null hypothesis (H0) and compatible with the ≥ 18% target (H1). Median OS was 12.8 months (95% CI 5.2-NR); 12-month OS was 58.3% (95% CI 27.0-80.1). ORR was 50.0%, and DCR was 91.7%. All three patients with untreated brain metastases achieved complete intracranial response. Toxicities were mainly grade 1-2; 41.7% had grade 3 adverse events; three discontinued durvalumab for immune-related toxicity; and no treatment-related deaths occurred.</p><p><strong>Conclusions: </strong>This first prospective evaluation of durvalumab + EP in aLCNEC, though underpowered, demonstrates efficacy and safety consistent with design expectations.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148304012","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":"\"Tumor Immunology Meets Oncology\" (TIMO), 22 May-24 May 2025 in Brandenburg an der Havel, Germany.","authors":"Barbara Seliger","doi":"10.1007/s00262-026-04468-y","DOIUrl":"10.1007/s00262-026-04468-y","url":null,"abstract":"<p><p>The \"Tumor Immunology Meets Oncology\" (TIMO XIX) meeting 2025 reports on the rapidly growing field of basic, but in particular translational tumor immunology thereby providing deeper insights into the heterogeneity of tumors, their microenvironment and clinical relevance. This represents the basis for the development of novel immunotherapeutic strategies and combinatorial therapies.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13315368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148311281","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":"Restoring STING expression in soft tissue sarcoma increases activation and function of tumor-infiltrating lymphocytes.","authors":"Stine Høvring Godsk, Mireia Cruz De Los Santos, Tobias Wang Bjerg, Thomas Gravgaard Andersen, Felix Haglund de Flon, Maria Elisabeth Harder, Anders Etzerodt, Ninna Aggerholm-Pedersen, Andreas Lundqvist, Martin Roelsgaard Jakobsen","doi":"10.1007/s00262-026-04455-3","DOIUrl":"10.1007/s00262-026-04455-3","url":null,"abstract":"<p><p>Sarcomas are rare, highly heterogeneous malignancies, with soft tissue sarcomas (STS) comprising nearly 80 histological subtypes. Localized STS is generally treated with surgery and radiotherapy, whereas metastatic disease relies largely on chemotherapy, which offers limited benefit. Although inflammation influences tumor development, treatment response, and prognosis, immune checkpoint inhibitors have shown minimal efficacy in sarcoma. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is linked to mutational burden, genomic instability, immune cell infiltration, and therapeutic response across multiple cancer types. However, its role in sarcoma remains unclear. In a newly established cohort of STS patients, we found that STING expression in primary tumors correlates with immune cell infiltration. Using a lipid nanoparticle (LNP)-mediated delivery of CRISPR activation mRNA components, we restored STING expression in STS cells, thereby reactivating cGAS-STING signaling. This promoted T‑cell recognition and tumor cell killing in both 2D and 3D patient-derived models and enhanced responses to anti-PD-1 treatment. Together, our results show that controlled epigenetic activation of STING in STS enhances immune infiltration and tumor cell killing. Targeting STING through CRISPR activation may therefore represent a promising therapeutic strategy for STS.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148298627","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":"Smoking-associated modulation of gut microbiota shapes response to immune checkpoint inhibitors in non-small cell lung cancer.","authors":"Po-Yu Chien, Wen-Chien Cheng, Chin-Chuan Hung, Chih-Yen Tu, Te-Chun Hsia, Der-Yang Cho, Po-Ren Hsueh, Zi-Lun Lai, Yi-Cheng Shen, Yu-Chao Lin","doi":"10.1007/s00262-026-04463-3","DOIUrl":"10.1007/s00262-026-04463-3","url":null,"abstract":"<p><strong>Background: </strong>Smoking status has been associated with differences in immune checkpoint inhibitor (ICI) efficacy in non-small cell lung cancer (NSCLC), though the underlying mechanisms remain unclear. This prospective cohort study evaluated whether smoking-related changes in the gut microbiota are linked to ICI response.</p><p><strong>Methods: </strong>Baseline fecal samples from 225 patients with NSCLC were analyzed using full-length 16S rRNA sequencing. Microbial composition, predicted functional features, and clinical variables were examined in relation to treatment response and progression-free survival (PFS). Associations with treatment response were assessed using multivariable ordinal logistic regression. PFS was evaluated using Kaplan-Meier analysis and the log-rank test.</p><p><strong>Results: </strong>Smoking was associated with selected taxon-level microbial differences despite no significant differences in alpha or beta diversity. Compared with never-smokers, smokers exhibited reduced abundance of Bifidobacterium longum and enrichment of Gram-negative taxa. Functional prediction indicated increased potential for lipopolysaccharide, Kdo₂-lipid A, and lipid IVA biosynthesis in smokers. Predicted lpxM abundance, encoding a lipid A myristoyltransferase, was positively correlated with the Gram-negative bacterial fraction. Moreover, increased abundance of lpxM-linked Gammaproteobacteria was associated with improved ICI response in the NSCLC cohort. Conversely, lower B. longum abundance was associated with favorable ICI response and prolonged PFS.</p><p><strong>Conclusions: </strong>These results indicate that smoking-related gut microbial alterations, particularly reduced B. longum abundance, are associated with enhanced ICI efficacy in NSCLC, supporting a role for the gut microbiota in smoking-associated differences in immunotherapy outcomes.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148298693","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":"Oncolytic virus with an immune stimulatory payload for osteosarcoma therapy.","authors":"Sumbul Khan, Theresa A Higgins, Isabella Shimko-Lofano, Maninder Sandey, Emma Logsdon, Gracie Bunch, Yasin Fatemi, Leah M K Hoffman, Bruce F Smith, Payal Agarwal","doi":"10.1007/s00262-026-04458-0","DOIUrl":"10.1007/s00262-026-04458-0","url":null,"abstract":"<p><p>Osteosarcoma (OS) is a highly aggressive bone malignancy that predominantly affects children and young adults. There have been no major changes in patient survival in the past four decades. Therefore, new therapeutic interventions are needed. We have developed an enhanced conditionally replicative canine oncolytic adenovirus, CAV2-AU-M3, armed with an anti-PD1 heavy-chain antibody (HcAb), and evaluated its efficacy against osteosarcoma across four canine cell lines. CAV2-AU-M3 was characterized for its infectivity, lytic properties, and anti-PD1 Ab production in monolayer and spheroid cultures. Additionally, the impact of intratumoral administration of the virus on tumor growth was measured in a mouse model. Our study demonstrates that CAV2-AU-M3 infects and lyses different canine OS cell lines at varying rates but produces anti-PD1 Ab at similar levels across all osteosarcoma cell lines. Additionally, anti-PD1 Ab produced by CAV2-AU-M3 can effectively bind the cell surface PD1 receptor and inhibit the binding of PDL1 to PD1 receptors.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148298680","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}