Cancer immunology, immunotherapy : CII最新文献

{"title":"Is adjuvant immunotherapy necessary after neoadjuvant chemoimmunotherapy in patients with resectable stage III NSCLC? A two-center real-world study.","authors":"Song Guan, Hui Wang, Zhaoxin Chen, Fengrui Guo, Guozhen Yi, Xingyu Du, Jingjing Yan, Cuimeng Tian","doi":"10.1007/s00262-025-04130-z","DOIUrl":"https://doi.org/10.1007/s00262-025-04130-z","url":null,"abstract":"<p><strong>Purpose: </strong>The value of adjuvant immunotherapy in patients with resectable stage III non-small cell lung cancer (NSCLC) after neoadjuvant chemoimmunotherapy remains unclear. This study aimed to evaluate the prognostic impact of additional adjuvant immunotherapy in patients with stage III NSCLC.</p><p><strong>Methods: </strong>Patients with stage III NSCLC who received neoadjuvant chemoimmunotherapy followed by radical surgery, with or without adjuvant immunotherapy, were retrospectively enrolled across two hospitals. Event-free survival (EFS) and overall survival (OS) were assessed from the initiation of neoadjuvant treatment and were estimated by the Kaplan‒Meier method. One-to-one propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to minimize confounding.</p><p><strong>Results: </strong>A total of 184 eligible patients were enrolled, of whom 105 (57.1%) received adjuvant immunotherapy and 79 (42.9%) did not. After 1:1 PSM, the addition of adjuvant immunotherapy did not significantly improve EFS (2-year EFS: 62.3% vs. 66.1%, P = 0.653) or OS (2-year OS: 92.7% vs. 89.6%, P = 0.196). Subgroup analyses, stratified by the pathological complete response (pCR) status, further confirmed that adjuvant immunotherapy did not significantly improve survival in either the pCR subgroup or the non-pCR subgroup. Similar results were obtained after IPTW. Exploratory analysis revealed that 3 cycles of neoadjuvant immunotherapy might be more beneficial than 2 (pCR: 40.8% vs. 30.6%, P = 0.292; 2-year EFS: 75.0% vs. 54.5%, P = 0.111) or 4 (pCR: 42.1% vs. 36.8%, P = 0.740; 2-year EFS: 63.2% vs. 51.5%, P = 0.343) cycles.</p><p><strong>Conclusion: </strong>The addition of adjuvant immunotherapy to neoadjuvant chemoimmunotherapy may not be necessary in patients with resectable stage III NSCLC. Three cycles of neoadjuvant immunotherapy appear to be an appropriate treatment regimen for neoadjuvant chemoimmunotherapy.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"273"},"PeriodicalIF":0.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677197","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":"Comprehensive analysis of exosome-related gene signature in multiple myeloma prognosis and immune microenvironment evaluation.","authors":"Dong Zheng, Bingxin Zhang, Quanqiang Wang, Sisi Zheng, Yibo Xia, Ziwei Zheng, Zhili Lin, Shuxia Zhu, Xinyi Zhang, Luning Cui, Hansen Ying, Tianyu Zhang, Shujuan Zhou, Zixing Chen, Enqing Lan, Yu Zhang, Xuanru Lin, Jingjing Chen, Honglan Qian, Xudong Hu, Yan Zhuang, Zuoting Xie, Xiangjing Zhou, Zhouxiang Jin, Songfu Jiang, Yongyong Ma","doi":"10.1007/s00262-025-04097-x","DOIUrl":"10.1007/s00262-025-04097-x","url":null,"abstract":"<p><p>Multiple myeloma (MM) is a genetically complicated plasma cell malignancy characterized by malignant plasma cell proliferation and monoclonal immunoglobulin synthesis. As a disease that remains incurable, enhancing prognostic accuracy is of paramount importance. Tumor-derived exosomes (TDEs) play key roles in modulating the tumor microenvironment, angiogenesis and immune system. Exosomes are involved in multiple processes contributing to cancer progression, including in MM. However, the connection between myeloma and exosome-related genes (ERGs) has not been explored. Therefore, we aim to establish a more accurate model to evaluate the prognosis of MM patients based on the exosome-related genes. This study established an ERG-based prognostic model for MM and investigated its association with the immune microenvironment. Using transcriptomic data from GSE136337 (training set) and GSE24080 (validation set), we identified six prognostic ERGs (BIRC5, LDHA, MRPS30, MRPL15, RPL26L1, and S1PR2) through Cox and LASSO regression analyses, constructing a risk-scoring model. The model demonstrated robust predictive performance for 3-year survival (AUC = 0.74 in training set; AUC = 0.69 in both validation sets). A nomogram integrating age, ISS stage, and risk score significantly improved prognostic accuracy (3-year survival AUC = 0.77). Functional enrichment analysis revealed that high-risk patients exhibited activation of oncogenic pathways, including cell cycle regulation and DNA replication (P < 0.01). Immune profiling identified an immunosuppressive microenvironment in the high-risk group, characterized by reduced CD8 + T cell infiltration (P = 0.004) and elevated TIDE scores (P = 0.012), indicating increased resistance to immunotherapy. TCGA database validation and in vitro experiments confirmed the critical role of these ERGs in tumor microenvironment remodeling. To our knowledge, this represents the first ERG-based prognostic system for MM, providing a biologically insightful and clinically applicable tool for personalized treatment strategies.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"269"},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645072","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":"Local-regional therapy combined with immune checkpoint inhibitors and lenvatinib versus immune checkpoint inhibitors plus chemotherapy in advanced intrahepatic cholangiocarcinoma: a multicenter cohort study.","authors":"Shuofeng Li, Guanhua Yu, Mingming Wang, Shi Feng, An Zhang, Yu Wu, Zixiang Zhou, Shanshan Wang, Yihong Zhang, Mingjian Piao, Chengjie Li, Ziyu Xun, Boyu Sun, Jiongyuan Li, Nan Zhang, Hu Li, Yongliang Sun, Wen Zhang, Zhenyu Zhu, Haitao Zhao","doi":"10.1007/s00262-025-04129-6","DOIUrl":"10.1007/s00262-025-04129-6","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy combined with immune checkpoint inhibitors (ICIs) remains the first-line treatment for advanced intrahepatic cholangiocarcinoma (ICC) but is limited by suboptimal efficacy. While local-regional therapy plus ICIs and lenvatinib (triple therapy) has demonstrated antitumor activity in biliary tract cancers, its role in ICC remains unclear. This multicenter study compared the effectiveness and tolerability of this triple therapy versus chemotherapy plus ICIs in advanced ICC.</p><p><strong>Methods: </strong>Advanced ICC patients receiving first-line local-regional therapy (radiotherapy, hepatic arterial infusion chemotherapy, or transarterial chemoembolization) plus ICIs and lenvatinib or chemotherapy plus ICIs were screened. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), adverse events (AEs).</p><p><strong>Results: </strong>A total of 78 patients receiving triple therapy and 70 patients receiving chemotherapy plus ICIs were included. The triple therapy group exhibited significantly prolonged median PFS (10.8 vs. 7.6 months, P = 0.011) and median OS (18.5 vs. 15.0 months, P = 0.040), along with higher ORR (51.3% vs. 27.1%) and DCR (85.9% vs. 81.4%). Grade 3-4 AEs occurred more frequently in the triple therapy group (60.3% vs. 58.6%), this difference lacked statistical significance (P = 0.968). No grade 5 events were reported, and all AEs were manageable. Multivariate analysis identified CEA as an independent prognostic factor for PFS and OS.</p><p><strong>Conclusion: </strong>Local-regional therapy plus ICIs and lenvatinib demonstrated superior efficacy and manageable toxicity, establishing it as a viable first-line regimen for advanced ICC.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"271"},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645176","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":"Anti-TIGIT therapies: a review of preclinical and clinical efficacy and mechanisms.","authors":"Erin C Sundstrom, Xueting Huang, Andrew J Wiemer","doi":"10.1007/s00262-025-04128-7","DOIUrl":"10.1007/s00262-025-04128-7","url":null,"abstract":"<p><p>TIGIT (T cell immunoreceptor with Ig and ITIM domains) has garnered interest as a next-generation anti-cancer immunotherapy target, yet its development has been marred by recent clinical failures. This review explores clinical and preclinical studies on TIGIT, examining antibody therapies, co-targeting with other checkpoint inhibitors, mechanistic signaling models, and the role of the Fc region. Here, we discuss how preclinical studies have found antitumor effects from anti-TIGIT antibodies, in particular when using the Fc competent mIgG2 scaffold in combination with anti-PD-1 in smaller-sized tumors. Yet, human monotherapy trials with IgG1 anti-TIGIT have disappointed. We investigate the extent to which combining anti-TIGIT with other treatments (primarily anti-PD-1) improves effectiveness, showing a clear benefit to co-targeting TIGIT, especially in patients positive for PD-L1 expression. We also discuss the Fc region, which has been thought to enhance success through mechanisms like myeloid cell activation, DC modification, and/or Treg depletion, but also risks targeting exhausted T cells for destruction, rather than activating them. The current evidence supports that TIGIT remains an interesting target, especially in Fc silent format, but expectations should be tempered, and research should focus on TIGIT blockade in combination with PD-1 blockade and how to best apply this combination.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"272"},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645161","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":"Concurrent treatment with transarterial immunoembolization of hepatic metastases and systemic immune checkpoint inhibitors to overcome immune evasion in patients with metastatic uveal melanoma.","authors":"Natalie J Miller, Sharon W Kwan, Jacob B Leary, Daniel S Hippe, William McCamy, Joshua R Veatch, Evan T Hall, Wayne L Monsky, Shailender Bhatia","doi":"10.1007/s00262-025-04124-x","DOIUrl":"10.1007/s00262-025-04124-x","url":null,"abstract":"<p><strong>Background: </strong>Metastatic uveal melanoma (mUM) is an uncommon melanoma subtype, poorly immunogenic with low objective response rates (ORR) to immune checkpoint inhibitors (ICI). Liver-directed therapies (LDT) are commonly used given the strong predilection for hepatic metastases. Transarterial immunoembolization (TAIE) with granulocyte-macrophage colony stimulating factor (GM-CSF) can potentially synergize with concurrent systemic ICI to overcome immune evasion.</p><p><strong>Methods: </strong>This single-center, retrospective study includes mUM patients with liver-predominant metastases who received TAIE, with/without concurrent systemic ICI (≤ 3 months before/during TAIE). Endpoints included ORR, progression-free survival (PFS), overall survival (OS), and adverse events (AEs).</p><p><strong>Results: </strong>Between 2016 and 2023, 18 mUM patients (median age 64 years) received TAIE (median 4 procedures/patient). Fourteen patients (78%) received concurrent ICI. ORR was 17% (3/18), all in patients receiving ICI, with partial responses lasting 4.2, 35 + and 46 months. Disease control rate (stable disease or better) was 56% (10/18). Median time to next systemic therapy or death was 19.5 months (range 1.6- 46). Median PFS and OS from first TAIE treatment were 4.9 months (range 0.7-46) and 35 months (range 1.7- 46). Immune-related AEs (IRAE) during concurrent therapy occurred in seven of 10 patients receiving anti-CTLA-4/PD-1 combination, including hepatitis (n = 5; grade 2 in 1, grade 3 in 4). Four of seven patients resumed anti-PD-1 monotherapy without recurrent IRAE.</p><p><strong>Conclusions: </strong>Concurrent LDT with GM-CSF TAIE and ICI, including anti-CTLA-4/PD-1 combination, is feasible, safe, and can lead to sustained clinical benefit in a subset of mUM patients. OS with this combination compares favorably to published outcomes for systemic therapy or LDT alone.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"270"},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645073","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":"Pre-clinical safety and efficacy evaluation of Helicobacter Pylori neutrophil-activating protein (NAP)-armed CAR-T cells targeting B cell lymphomas.","authors":"Jing Ma, Tina Sarén, Chuan Jin, Hyeong Su Kim, Paola Donaji Contreras Pineda, Marina de Bernard, Rose-Marie Amini, Veronica Rondahl, Gunilla Enblad, Di Yu, Magnus Essand","doi":"10.1007/s00262-025-04112-1","DOIUrl":"10.1007/s00262-025-04112-1","url":null,"abstract":"<p><p>CD19 CAR-T cell therapy shows striking results in treating B cell malignancies. However, approximately two-thirds of the lymphoma patients eventually relapse, with about one-third displaying CD19-negative tumors at relapse. Our previous study showed that CAR-T cells armed with the Helicobacter pylori neutrophil-activating protein (NAP), CAR(NAP)-T cells, can trigger a bystander immune response and eliminate CAR-target-antigen-negative tumor cells. Here, we report the development of CD20-targeted CAR-T cells (CAR20-T cells), with the targeting moiety from rituximab, and the safety and efficacy of NAP-armed CAR-T cells. CAR20-T cells displayed efficient and specific cytotoxic potential against multiple human B cell lymphoma cell lines in vitro. In addition, primary mantle cell lymphoma cells, isolated from a patient who relapsed after rituximab treatment, can also be eliminated by CAR20-T cells. CAR20(NAP)-T cells delayed tumor growth and prolonged survival of mice with lymphoma. No obvious histopathological alteration in major organs were observed in mice treated with CAR(NAP)-T cells. Further, no excessive cytokine release or immune cell activation was observed when human blood from healthy volunteers was exposed to recombinant NAP protein in an ex vivo blood loop assay, suggesting a safe therapeutic profile for NAP. Taken together, these results warrant the clinical investigation of CAR20(NAP)-T cells.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"262"},"PeriodicalIF":0.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621649","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":"Single-cell RNA sequencing and multi-omics analysis of prognosis-related staging in papillary thyroid cancer.","authors":"Guo Ji, Hanlin Sun, Simo Chen, Xuechen Sun, Le Chang, Ruting Xie, Runzhi Huang, Lijun Zheng, Zhengyan Chang","doi":"10.1007/s00262-025-04101-4","DOIUrl":"10.1007/s00262-025-04101-4","url":null,"abstract":"<p><strong>Background: </strong>Papillary thyroid cancer (PTC) is the most common thyroid cancer, but current molecular features inadequately stratify its risk. Whether distinct underlying mechanisms can further classify PTC and improve prognostic precision remains unclear.</p><p><strong>Methods: </strong>We integrated single-cell RNA sequencing data (158,577 cells from 11 PTC patients; GEO: GSE184362) with bulk-RNA sequencing data from The Cancer Genome Atlas Thyroid Carcinoma (TCGA-THCA) cohort (501 patients). Multi-omics analyses were employed to elucidate PTC heterogeneity, identify malignant cell differentiation and prognosis-related genes (MCD&PRGs), and construct a novel molecular classification, the Oncogenic Signature Of Papillary Thyroid Carcinoma Classification (OSPTCC). A prognostic risk score was developed, and the classification's prognostic relevance was further explored in an independent institutional cohort using qRT-PCR.</p><p><strong>Results: </strong>Single-cell analysis revealed three malignant cell differentiation states (PTC1-3) and a 34-gene signature (MCD&PRGs). This formed the basis of our Oncogenic Signature Of Papillary Thyroid Carcinoma Classification (OSPTCC), defining three subtypes: Inflammation-associated (IPTCC), BRAF/autophagy-related (BAPTCC), and lipid metabolism-related (LPTCC). These subtypes showed distinct molecular profiles and significantly different progression-free survival (IPTCC poorest, P = 0.044). A 7-gene risk score derived from MCD&PRGs independently predicted prognosis (multivariate HR = 21.511, P < 0.001). qRT-PCR validation in an independent cohort (n = 48) using key markers (DEPTOR, APOE, APOC1) confirmed that OSPTCC-based risk stratification correlated with adverse clinical features, including higher recurrence rates in the high-risk group (P = 0.007).</p><p><strong>Conclusions: </strong>This study introduces OSPTCC, a prognostically significant molecular classification for PTC based on tumor cell differentiation states. The identified subtypes, characterized by distinct biological mechanisms, provide deeper insights into PTC's molecular pathology and offer a framework for improved risk stratification and potential precision therapies.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"267"},"PeriodicalIF":0.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621693","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":"TGF-β3 promotes vascular normalization of prostate cancer to potentiate immunotherapy and chemotherapy.","authors":"Qiliang Teng, Niu Wang, Hanqi Lei, Tongyu Tong, Yupeng Guan, Mengjun Huang, Fei Cao, Bin Xu, Jia Yang, Yimian Huo, Wenping Chen, Ran Bi, Xuanqi Wang, Zhenyu Wang, Fu-Ying Tian, Bo Zhao, Jun Pang","doi":"10.1007/s00262-025-04103-2","DOIUrl":"10.1007/s00262-025-04103-2","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PCa) has previously been established as a cold tumor with highly complex tumor environment. Transforming growth factor (TGF)-β1 plays pro-oncogenic roles in PCa. TGF-β3, another isoform of the TGF-β family, is reported to have different and even opposite regulatory roles to TGF-β1. However, the effect of TGF-β3 in PCa has not been elucidated.</p><p><strong>Methods: </strong>TGF-β3 expression and its association with multiple clinicopathological characteristics were analyzed immunohistochemically in human PCa specimens. The antitumor effect of TGF-β3 and its combination with immunochemotherapy was observed by subcutaneous xenograft tumor model. RNA-seq of mouse tumor tissues identified differentially expressed genes (DEGs) that were enriched in vascular biological processes. The angiogenesis effect of TGF-β3 was evaluated using tube formation assay. Hypoxic area, NG2⁺ pericytes, Col IV⁺ basement membrane, adhesion molecules and immune cells were analyzed by immunofluorescence. Vascular permeability was measured by Evans blue staining. The flow cytometry was conducted to examine the composition of tumor-infiltrating CD8⁺ T cells.</p><p><strong>Results: </strong>Low TGF-β3 expression in prostate cancer (PCa) was correlated with higher Gleason scores and pathological T stage. While intratumoral TGF-β3 injection demonstrated antitumor effects in vivo, it did not directly affect PCa cell proliferation, migration or invasion in vitro. GO analysis revealed significant enrichment of DEGs in vascular-related biological process. TGF-β3 treatment normalized tumor vascular architecture and reduced vascular leakage. This vascular normalization upregulated endothelial adhesion molecules and enhanced CD8⁺ T cell infiltration, suppressing tumor growth. Critically, TGF-β3-induced vascular normalization synergized with anti-PD-L1 immunotherapy or paclitaxel chemotherapy, enhancing CD8⁺ T cell or drug infiltration and significantly boosting therapeutic efficacy.</p><p><strong>Conclusions: </strong>TGF-β3 potentially acts as a protective factor in PCa by promoting vascular normalization and remodeling of the tumor environment, which facilitates infiltration of CD8⁺ T cells or drugs, significantly enhancing their antitumor effects.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"268"},"PeriodicalIF":0.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A high proportion of CD38 (high) CD16 (low) NK cells in colorectal cancer can interrupt immune surveillance and favor tumor growth.","authors":"Xueling Wang, Li Li, Xianqin Song, Kehua Fang, Xiaotian Chang","doi":"10.1007/s00262-025-04044-w","DOIUrl":"10.1007/s00262-025-04044-w","url":null,"abstract":"<p><p>CD38 + NK cells have been detected in many diseases. The present study investigated the mechanism of CD38 + NK cells in immune surveillance in tumors. Significant increases in the proportions of CD38 + NK cells were detected via flow cytometry in the peripheral blood of patients with breast cancer, colorectal cancer (CRC), esophageal cancer, gastric cancer (GC), lung cancer (LG) or ovarian cancer (OC). Transcriptomics and metabonomics revealed special expression profiles and metabolite abundance patterns in CRC CD38 + NK cells, especially decreased HSPA1 (heat shock 70 kDa protein 1A) and increased ADO (adenosine) levels. Compared with CD38 + NK cells from healthy individuals, CRC CD38 + NK cells presented lower NAD + (nicotinamide adenine dinucleotide) production, apoptosis-inducing ability and tumor cell killing ability, and higher infiltration into tumor tissues and tumor cell proliferation-inducing ability. CRC CD38 + NK cells also produce less TNF-alpha and more IL-2, ADO and TGF-beta. When the CD38 + NK cells were pretreated with anti-CD38 antibodies, the opposite results were obtained, and IFN-gamma production was increased. Wild-type C57BL/6 J mice grafted with mouse colon tumor-derived MC38 cells presented greater tumor growth, as well as higher Treg and CD38 + NK cell levels and lower Th1 cell levels in the peripheral blood than did the tumor-bearing model established with CD38 KO mice. Additionally, increased CD38, PD-1 and NF-kB expression and decreased CD16, Sirt1, Sirt6 and HSPA1 expression were detected in CRC CD38 + NK cells via real-time PCR and Western blot analysis, indicating that the NK cells expressed high CD38 and low CD16. High proportions of CD38 + CD16- NK cells were detected in the blood of CRC, GC, LC and OC patients. It is well known that high Tregs, TGF-beta, PD-1 and ADO levels, and low HSPA1, NAD + , TNF-alpha and IFN-gamma levels contribute to immune tumor cell escape. Our results suggest that a high proportion of CD38 (high) CD16 (low) NK cells in tumor patients can interrupt immune surveillance and favor tumor growth.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"263"},"PeriodicalIF":0.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621646","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":"Real-world effectiveness and safety of first-line chemoimmunotherapy combinations in metastatic non-small cell lung cancer with programmed death ligand-1 < 50%: results from an Italian observational study.","authors":"Alessandro Inno, Antonello Veccia, Ettore D'Argento, Floriana Morgillo, Elio Gregory Pizzutilo, Fabiana Vitiello, Alberto Pavan, Fiorella Lombardo, Marco Russano, Vincenzo Sforza, Francesca Colamartini, Carlo Genova, Rita Chiari, Antonella Cristofano, Alessandro Delconte, Emanuela Vattemi, Alessandra Dessi, Daniele Galanti, Simona Busato, Giovanni Palazzolo, Clementina Savastano, Antonio Bianco, Francesco Verderame, Cristina Mazzi, Fabiana Marchetti, Stefania Kinspergher, Denis Occhipinti, Carminia Maria Della Corte, Daniele Piscazzi, Marina Gilli, Emilio Bria, Orazio Caffo, Stefania Gori","doi":"10.1007/s00262-025-04125-w","DOIUrl":"10.1007/s00262-025-04125-w","url":null,"abstract":"<p><strong>Introduction: </strong>This multi-center, observational cohort study aimed to evaluate the real-world effectiveness and safety of two first-line chemoimmunotherapy combinations-pembrolizumab plus chemotherapy and nivolumab/ipilimumab plus chemotherapy-in patients with metastatic non-small cell lung cancer (NSCLC) and programmed death ligand-1 (PD-L1) expression < 50%.</p><p><strong>Patients and methods: </strong>The primary objectives were progression-free survival (PFS) and overall survival (OS) in the overall population. Secondary objectives included the incidence of chemotherapy-related and immune-related adverse events (irAEs).</p><p><strong>Results: </strong>A total of 495 patients were enrolled, with 348 (70.3%) receiving pembrolizumab plus chemotherapy and 147 (29.7%) treated with nivolumab/ipilimumab plus chemotherapy. Overall, median follow-up was 11 (95% CI: 10.2 12.2) months. The median PFS was 10.9 months (95% CI: 9.6-13), and the median OS was 21.1 months (95% CI: 16.8-NR) in the overall population. In multivariable analysis, ECOG PS ≥ 2, PD-L1 expression < 1%, squamous histology, baseline steroid use, and the presence of CNS, bone, or liver metastases were significantly associated with shorter survival. No significant differences were observed between the pembrolizumab and nivolumab/ipilimumab cohorts in terms of PFS (11.83 vs. 9.83 months; HR 0.86, 95% CI: 0.67-1.11, p = 0.3) or OS (21.3 vs. 20.6 months; HR 1.03, 95% CI: 0.76-1.39, p = 0.9). Chemotherapy-related adverse events were more frequent in the pembrolizumab cohort, whereas irAEs were more common in the nivolumab/ipilimumab cohort.</p><p><strong>Conclusion: </strong>In this real-world study, chemoimmunotherapy combinations demonstrated manageable toxicity profiles, with effectiveness comparable to that reported in pivotal phase 3 randomized trials. Pembrolizumab and nivolumab/ipilimumab showed similar real-world effectiveness but significantly different toxicity profiles.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 8","pages":"266"},"PeriodicalIF":0.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621650","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}