Cancer Immunology, Immunotherapy最新文献

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Ruxolitinib stopped before transplantation does not induce cytokine release in myelofibrosis. 移植前停用Ruxolitinib不会诱导骨髓纤维化的细胞因子释放。
IF 4.6 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2025-04-24 DOI: 10.1007/s00262-025-04046-8
Sara Villar, Emmanuel Curis, Marie-Hélène Schlageter, Nelly Bosselut, Amandine Charbonnier, Marie-Thérèse Rubio, Pascal Turlure, Hélène Labussière, Jacques-Olivier Bay, Jérome Cornillon, Laure Vincent, Corentin Orvain, Jean-Jacques Kiladjian, David Michonneau, Gérard Socié, Marie Robin
{"title":"Ruxolitinib stopped before transplantation does not induce cytokine release in myelofibrosis.","authors":"Sara Villar, Emmanuel Curis, Marie-Hélène Schlageter, Nelly Bosselut, Amandine Charbonnier, Marie-Thérèse Rubio, Pascal Turlure, Hélène Labussière, Jacques-Olivier Bay, Jérome Cornillon, Laure Vincent, Corentin Orvain, Jean-Jacques Kiladjian, David Michonneau, Gérard Socié, Marie Robin","doi":"10.1007/s00262-025-04046-8","DOIUrl":"10.1007/s00262-025-04046-8","url":null,"abstract":"<p><p>Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by marrow fibrosis, splenomegaly, constitutional symptoms and cytopenia with a proinflammatory and profibrotic cytokine phenotype involving the JAK-STAT pathway. Ruxolitinib is a JAK 1/2 inhibitor with proven efficacy on splenomegaly and constitutional symptoms, but it does not reverse fibrosis or the risk of leukemic transformation. While hematopoietic stem cell transplantation remains the only curative approach, it is still associated with a relatively high non-relapse mortality (NRM) rate, partly due to GVHD. The potential role of ruxolitinib or its withdrawal on NRM remains to be elucidated, and inflammatory cytokines might be implicated. In this report, we compared cytokine profiles in patients with myelofibrosis not treated with ruxolitinib (n = 18) or who received ruxolitinib and stopped it at conditioning regimen initiation (n = 53), at three different time points. At baseline, MF patients without ruxolitinib had increased inflammatory cytokine levels (CD25, REG3A, IL18 and ST2) as compared to MF patients on ruxolitinib. On day 0 and week 1 post-transplantation, levels of these cytokines were similar with and without ruxolitinib. On the other hand, cytokine levels at baseline did not predict grades 2-4 acute GVHD or hyperacute GVHD. These findings suggest that baseline cytokine profile in MF patients does not impact the risk of GVHD. Stopping ruxolitinib just before conditioning regimen may not influence GVHD risk more than in MF patients who have not received ruxolitinib. The potential benefit of a later ruxolitinib discontinuation on D0 or after transplantation ruxolitinib requires further investigation.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"181"},"PeriodicalIF":4.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12022196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
USP5 motivates immunosuppressive microenvironment in multiple myeloma by activating STAT2-PFKFB4-mediated glycolysis. USP5通过激活stat2 - pfkfb4介导的糖酵解激活多发性骨髓瘤的免疫抑制微环境。
IF 4.6 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2025-04-24 DOI: 10.1007/s00262-025-04031-1
Shifeng Long, Ting Ding, Yongliang Zheng, Jinmei Shao, Yan Liu, Qinglan Wang
{"title":"USP5 motivates immunosuppressive microenvironment in multiple myeloma by activating STAT2-PFKFB4-mediated glycolysis.","authors":"Shifeng Long, Ting Ding, Yongliang Zheng, Jinmei Shao, Yan Liu, Qinglan Wang","doi":"10.1007/s00262-025-04031-1","DOIUrl":"10.1007/s00262-025-04031-1","url":null,"abstract":"<p><strong>Background: </strong>Glycolysis, a classic characteristic of cancer cells, can drive cancer progression by generating lactate, which play as a key immunosuppressive mediator. Currently, ubiquitin-specific proteases 5 (USP5) has been demonstrated to facilitate tumor cell survival in multiple myeloma (MM), whereas whether USP5 was involved in glycolysis-lactate production pathway and immunosuppressive microenvironment formation in MM remain unknown.</p><p><strong>Methods: </strong>The gene and protein expression characteristics were assessed via qRT-PCR and western blot. MM cell survival was determined by CCK-8 and flow cytometry analysis. Glycolysis was evaluated by examining glucose uptake, lactate production and ATP level via corresponding kits. Tumor-associated macrophages polarization was tested via measurement of M1/M2-like macrophage markers using qRT-PCR and flow cytometry methods. Dual-luciferase reporter, chromatin immunoprecipitation and co-immunoprecipitation assays were conducted to verified molecular relationship. Xenograft model was used for verified cellular findings.</p><p><strong>Results: </strong>USP5 was abnormally overexpressed in MM patients and cell lines. Knockdown of USP5 could restrain MM cell survival and glycolysis activity, thus reducing lactate-mediated immunosuppressive M2-like macrophage polarization in vitro and in vivo, whereas overexpression of USP5 play opposite impacts. Mechanistically, USP5 could downregulate the ubiquitination modification of STAT to stabilize STAT2 protein, thus activating PFKFB4 transcription. Moreover, STAT2 could overturn the regulatory role of USP5 on MM cell survival, glycolysis and lactate-mediated immunosuppressive M2-like macrophage polarization.</p><p><strong>Conclusion: </strong>These findings elucidated that USP5 served as a regulator of glycolysis-lactate to stimulate M2-like macrophage formation by regulating STAT2-PFKFB4 signaling, which supported that USP5 could be a viable therapeutic target of MM treatment.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"180"},"PeriodicalIF":4.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12022197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Combination of immune checkpoint inhibitors and anthracyclines as a potential first-line regimen for dedifferentiated liposarcoma: systematic review and meta-analysis. 免疫检查点抑制剂联合蒽环类药物作为去分化脂肪肉瘤的潜在一线治疗方案:系统评价和荟萃分析
IF 4.6 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2025-04-21 DOI: 10.1007/s00262-025-04007-1
Zhuang Aobo, Zhou Xiao, Xu Chengfei, Xi Zhe, Chen Yingxue, Zhang Chenhe, Xie Fuan, Yang Fan, Xiao Mengmeng, Ye Feng, Li Wengang
{"title":"Combination of immune checkpoint inhibitors and anthracyclines as a potential first-line regimen for dedifferentiated liposarcoma: systematic review and meta-analysis.","authors":"Zhuang Aobo, Zhou Xiao, Xu Chengfei, Xi Zhe, Chen Yingxue, Zhang Chenhe, Xie Fuan, Yang Fan, Xiao Mengmeng, Ye Feng, Li Wengang","doi":"10.1007/s00262-025-04007-1","DOIUrl":"10.1007/s00262-025-04007-1","url":null,"abstract":"<p><strong>Introduction: </strong>Dedifferentiated liposarcoma (DDLPS) is a rare and aggressive subtype of soft tissue sarcoma, characterized by limited treatment options and poor prognosis. Despite surgical resection being the only potentially curative treatment for localized DDLPS, the recurrence rate remains high, and systemic chemotherapy, typically anthracycline-based, shows limited efficacy in advanced stages. While immune checkpoint inhibitors (ICIs) have shown promise in various sarcoma subtypes, including DDLPS, their role as a first-line treatment remains unclear.</p><p><strong>Methods: </strong>We conducted a systematic meta-analysis to evaluate the efficacy of ICIs in treating patients with DDLPS. A total of 25 studies encompassing 245 patients were included. Data on overall response rate (ORR), progression-free survival, and grade III-V treatment-related adverse events were analyzed. We assessed treatment efficacy based on the line of therapy and treatment regimens, including ICI monotherapy, dual ICI therapy, and ICI combinations with other modalities.</p><p><strong>Results: </strong>The pooled ORR for all ICI-based treatments was 7%. First-line ICI therapy yielded a significantly higher ORR of 22%, compared to 4% in later-line treatment. The combination of ICI with anthracyclines demonstrated the highest ORR of 52%. In contrast, ICI regimens combined with trabectedin or other agents showed limited efficacy. Sensitivity analysis confirmed the stability of results, and publication bias was not detected.</p><p><strong>Conclusion: </strong>This meta-analysis supports the potential role of ICIs, particularly in combination with anthracyclines, as a first-line therapeutic strategy for DDLPS. These results provide a foundation for future prospective studies aimed at optimizing immunotherapy approaches for this rare and challenging malignancy.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"179"},"PeriodicalIF":4.6,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction: Efficacy and safety of lenvatinib combined with anti-PD-1 antibodies plus GEMOX chemotherapy as non-first-line systemic therapy in advanced gallbladder cancer. 修正:lenvatinib联合抗pd -1抗体+ GEMOX化疗作为非一线全身治疗晚期胆囊癌的疗效和安全性。
IF 4.6 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2025-04-21 DOI: 10.1007/s00262-025-03999-0
Yang Tan, Kai Liu, Chengpei Zhu, Shanshan Wang, Yunchao Wang, Jingnan Xue, Cong Ning, Nan Zhang, Jiashuo Chao, Longhao Zhang, Junyu Long, Xiaobo Yang, Daobing Zeng, Lijin Zhao, Haitao Zhao
{"title":"Correction: Efficacy and safety of lenvatinib combined with anti-PD-1 antibodies plus GEMOX chemotherapy as non-first-line systemic therapy in advanced gallbladder cancer.","authors":"Yang Tan, Kai Liu, Chengpei Zhu, Shanshan Wang, Yunchao Wang, Jingnan Xue, Cong Ning, Nan Zhang, Jiashuo Chao, Longhao Zhang, Junyu Long, Xiaobo Yang, Daobing Zeng, Lijin Zhao, Haitao Zhao","doi":"10.1007/s00262-025-03999-0","DOIUrl":"10.1007/s00262-025-03999-0","url":null,"abstract":"","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"178"},"PeriodicalIF":4.6,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prognostic nutrition index reveals LAG3 in cytotoxic CD8+ T cells and MHC class II in gastric cancer cells. 预后营养指数显示细胞毒性CD8+ T细胞中存在LAG3,胃癌细胞中存在MHC II类。
IF 4.6 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2025-04-19 DOI: 10.1007/s00262-025-04037-9
Chikanori Tsutsumi, Kenoki Ohuchida, Masaki Imamura, Bryan Tan, Yuki Shimada, Kiwa Son, Takaaki Kosai, Naoki Katayama, Yuki Mochida, Sayuri Hayashida, Chika Iwamoto, Nobuhiro Torata, Kohei Horioka, Koji Shindo, Yusuke Mizuuchi, Naoki Ikenaga, Kohei Nakata, Yoshinao Oda, Masafumi Nakamura
{"title":"Prognostic nutrition index reveals LAG3 in cytotoxic CD8+ T cells and MHC class II in gastric cancer cells.","authors":"Chikanori Tsutsumi, Kenoki Ohuchida, Masaki Imamura, Bryan Tan, Yuki Shimada, Kiwa Son, Takaaki Kosai, Naoki Katayama, Yuki Mochida, Sayuri Hayashida, Chika Iwamoto, Nobuhiro Torata, Kohei Horioka, Koji Shindo, Yusuke Mizuuchi, Naoki Ikenaga, Kohei Nakata, Yoshinao Oda, Masafumi Nakamura","doi":"10.1007/s00262-025-04037-9","DOIUrl":"10.1007/s00262-025-04037-9","url":null,"abstract":"<p><strong>Background: </strong>The prognostic nutrition index (PNI) has recently been highlighted as a predictor of immune checkpoint (IC) inhibitor efficacy in gastric cancer (GC). Although LAG3, an IC molecule, has gained considerable attention, its association with PNI remains unexplored.</p><p><strong>Materials and methods: </strong>We retrospectively analyzed clinical data from 796 GC patients who underwent radical gastrectomy to identify which previously reported nutritional index had the greatest impact on prognosis. Single-cell RNA sequencing was performed on 38 GC tissues, and multiplex immunofluorescence staining was conducted on 59 GC tissues to evaluate the relationship between nutritional indices and IC molecule expression in cytotoxic CD8-positive T cells.</p><p><strong>Results: </strong>A low preoperative PNI was identified as the strongest predictor of poor prognosis among the nutritional indices in GC patients. The expression of not only PDCD1 (encoding PD1) but also LAG3 in cytotoxic CD8-positive T cells was significantly higher in GC with low PNI compared to those with high PNI. Among cytotoxic CD8-positive T cells, the proportion of LAG3-positive cells was greater than that of PDCD1-positive cells, particularly in GC with low PNI, and most LAG3-positive cells did not co-express PDCD1. Additionally, the expression of MHC class II, a ligand for LAG3, was higher in GC cells with high levels of epithelial-mesenchymal transition-related molecules in GC with low PNI compared to those with high PNI.</p><p><strong>Conclusions: </strong>PNI can reflect LAG3 expression in cytotoxic CD8-positive T cells and MHC class II expression in GC cells.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"176"},"PeriodicalIF":4.6,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12009253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143968752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification and validation of poor prognosis immunoevasive subtype of esophageal cancer with tumor-infiltrating SAMD3 + NK cell abundance. 肿瘤浸润SAMD3 + NK细胞丰度对食管癌不良预后免疫逃避亚型的鉴定与验证。
IF 4.6 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2025-04-19 DOI: 10.1007/s00262-025-04028-w
Xu Huang, Runze You, Fangyi Liu, Zitao Jian, Guanyou Zhou, Hao Yin, Mengyuan Wu, Tiantao Sun, Zhiyun Duan, Wenyi Xu, Shaoyuan Zhang, Xinyu Yang, Heng Jiao, Shuyi Yang, Qingle Wang, Jun Yin, Han Tang, Miao Lin, Lijie Tan
{"title":"Identification and validation of poor prognosis immunoevasive subtype of esophageal cancer with tumor-infiltrating SAMD3 + NK cell abundance.","authors":"Xu Huang, Runze You, Fangyi Liu, Zitao Jian, Guanyou Zhou, Hao Yin, Mengyuan Wu, Tiantao Sun, Zhiyun Duan, Wenyi Xu, Shaoyuan Zhang, Xinyu Yang, Heng Jiao, Shuyi Yang, Qingle Wang, Jun Yin, Han Tang, Miao Lin, Lijie Tan","doi":"10.1007/s00262-025-04028-w","DOIUrl":"10.1007/s00262-025-04028-w","url":null,"abstract":"<p><strong>Introduction: </strong>Esophageal cancer (EC) remains highly lethal due to tumor microenvironment (TME)-mediated immune evasion. While natural killer (NK) cells are central to antitumor immunity, their functional states in EC are poorly characterized.</p><p><strong>Methods: </strong>We integrated bulk RNA-seq (TCGA/GEO) and single-cell data to construct an NK cell-derived prognostic signature (NK score) via LASSO-Cox regression. Immunofluorescence was applied to assess the clinical relevance of SAMD3 + NK cells in EC. Using both xenograft mouse models and in vitro co-culture procedures, the impact of SAMD3 on NK cell function was confirmed.</p><p><strong>Results: </strong>In EC patients, the prognostic NK score-which is generated from important NK cell markers including SAMD3-was substantially correlated with a worse chance of survival. NK cells within the TME had significant levels of SAMD3 expression, as seen by immunofluorescence labeling. Moreover, NK cells with SAMD3 knockdown exhibited enhanced antitumor activity, leading to decreased tumor development in the xenograft model.</p><p><strong>Discussion: </strong>Our results demonstrate the predictive significance of NK cell markers in EC and pinpoint SAMD3 as a critical modulator of NK cell activity. We pioneer SAMD3 + NK cells as architects of TME immunosuppression in EC. Our findings nominate SAMD3 inhibition as a combinatorial strategy to overcome immune checkpoint blockade resistance.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"177"},"PeriodicalIF":4.6,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12009252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of SURF4 and RALGAPA1 as promising therapeutic targets in glioblastoma and pan-cancer through integrative multi-omics, CRISPR-Cas9 screening and prognostic meta-analysis. 通过整合多组学、CRISPR-Cas9筛查和预后meta分析,确定SURF4和RALGAPA1是胶质母细胞瘤和泛癌的有希望的治疗靶点。
IF 4.6 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2025-04-18 DOI: 10.1007/s00262-025-04034-y
Fei Wang, Yuxuan Chen, Run Huang, Dengfeng Lu, Juyi Zhang, Yanbo Yang, Hanhan Dang, Meirong Liu, Zhouqing Chen, Xiaoou Sun, Zhong Wang
{"title":"Identification of SURF4 and RALGAPA1 as promising therapeutic targets in glioblastoma and pan-cancer through integrative multi-omics, CRISPR-Cas9 screening and prognostic meta-analysis.","authors":"Fei Wang, Yuxuan Chen, Run Huang, Dengfeng Lu, Juyi Zhang, Yanbo Yang, Hanhan Dang, Meirong Liu, Zhouqing Chen, Xiaoou Sun, Zhong Wang","doi":"10.1007/s00262-025-04034-y","DOIUrl":"10.1007/s00262-025-04034-y","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most aggressive and malignant type of primary brain tumor, with a median survival time of less than two years and a uniformly poor prognosis, despite multimodal therapeutic approaches, which highlights an urgent need for novel therapeutic targets. In this study, by integrative multi-omics analysis from CPTAC database, DepMap database and seven independent GBM cohorts, four hub genes (CD44, SURF4, IGSF3 and RALGAPA1) were identified as essential genes regulated by cancer driver genes with robust prognostic value. GBM multi-omics data from public and in-house cohorts validated that CD44 and SURF4 might be synthetic lethal partners of loss-of-function tumor suppressor genes. Analysis for immune-related pathway activity revealed complex regulation relationships of the four hub genes in tumor microenvironment (TME). Further investigation on SURF4 in pathway activity, immune therapy response and drug sensitivity proposed that SURF4 emerged as a promising therapeutic target for GBM, even for pan-cancer. Pan-cancer multi-omics exploration suggested that RALGAPA1 may be a tumor suppressor gene. By screening the first-generation and second-generation DepMap database, four genes (CCDC106, GAL3ST1, GDI2 and HSF1) might be considered as synthetic targets after mutation of RALGAPA1 as a tumor suppressor gene.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"175"},"PeriodicalIF":4.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association of peripheral monocytic myeloid-derived suppressor cells with molecular subtypes in single-center endometrial cancer patients receiving carboplatin + paclitaxel/avelumab (MITO-END3 trial). 外周单核细胞髓源性抑制细胞与单中心子宫内膜癌患者接受卡铂+紫杉醇/avelumab分子亚型的关联(MITO-END3试验)
IF 4.6 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2025-04-17 DOI: 10.1007/s00262-025-04021-3
C D'Alterio, G Rea, M Napolitano, E Coppola, A Spina, D Russo, R Azzaro, C Mignogna, G Scognamiglio, D Califano, L Arenare, C Schettino, C Pisano, S C Cecere, M Di Napoli, A Passarelli, F Perrone, S Pignata, S Scala
{"title":"Association of peripheral monocytic myeloid-derived suppressor cells with molecular subtypes in single-center endometrial cancer patients receiving carboplatin + paclitaxel/avelumab (MITO-END3 trial).","authors":"C D'Alterio, G Rea, M Napolitano, E Coppola, A Spina, D Russo, R Azzaro, C Mignogna, G Scognamiglio, D Califano, L Arenare, C Schettino, C Pisano, S C Cecere, M Di Napoli, A Passarelli, F Perrone, S Pignata, S Scala","doi":"10.1007/s00262-025-04021-3","DOIUrl":"10.1007/s00262-025-04021-3","url":null,"abstract":"<p><p>The MITO-END3 trial compared carboplatin and paclitaxel (CP) with avelumab plus carboplatin and paclitaxel (CPA) as first-line treatment in endometrial cancer (EC) patients and demonstrated a significant interaction between avelumab response and mismatch repair status. To investigate prognostic/predictive biomarker, 29 MITO-END3-EC patients were evaluated at pretreatment (B1) and at the end of CP/CPA treatment (B2) for peripheral myeloid-derived suppressor cells (MDSC) and Tregs. At B2, effector Tregs frequency was significantly higher in patients treated with CPA as compared to CP (p = 0.038). Both treatments (CP/CPA) induced significant decrease in peripheral M-MDSC (- 5.41%) in TCGA 2-MSI-high as compared to TCGA-category 4 tumors (p = 0.004). In accordance, both treatments induced M-MDSCs (+ 5.34%) in MSS patients as compared to MSI-high patients (p = 0.001). Moreover, in a subgroup of patients, primary tumors were highly infiltrated by M-MDSCs in MSS as compared to MSI-high ECs. A post hoc analysis displayed higher frequency of M-MDSCs (p = 0.020) and lower frequency of CD4+ (p < 0.005) at pretreatment in EC patients as compared to healthy donors. In conclusion, the peripheral evaluation of MDSCs and Tregs correlated with molecular features in EC treated with CP/CPA and may add insights in identifying EC patients responder to first-line chemo/chemo-immunotherapy.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"172"},"PeriodicalIF":4.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Clinical and dynamic circulating cytokines profile features of long-term progression-free survival benefit to immune checkpoint inhibitors in advanced non-small cell lung cancer. 免疫检查点抑制剂治疗晚期非小细胞肺癌的临床和动态循环细胞因子特征的长期无进展生存获益
IF 4.6 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2025-04-17 DOI: 10.1007/s00262-025-03984-7
Jia-Yi Deng, Ming Gao, Xue Fan, Hong-Hong Yan, Wei-Chi Luo, Ming-Yi Yang, Xiao-Rong Yang, Zhi-Hong Chen, Chong-Rui Xu, Qing Zhou
{"title":"Clinical and dynamic circulating cytokines profile features of long-term progression-free survival benefit to immune checkpoint inhibitors in advanced non-small cell lung cancer.","authors":"Jia-Yi Deng, Ming Gao, Xue Fan, Hong-Hong Yan, Wei-Chi Luo, Ming-Yi Yang, Xiao-Rong Yang, Zhi-Hong Chen, Chong-Rui Xu, Qing Zhou","doi":"10.1007/s00262-025-03984-7","DOIUrl":"10.1007/s00262-025-03984-7","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) offer durable progression-free survival (PFS) benefit in a subset of patients with advanced non-small cell lung cancer (NSCLC). However, the predictors of long-term PFS (LTPFS) remain unclear.</p><p><strong>Methods: </strong>Advanced NSCLC patients receiving first-line ICIs monotherapy at Guangdong Lung Cancer Institute between December 2017 and August 2022 were identified. Predictive value of different characteristics was evaluated in LTPFS (PFS ≥ 24 months) compared with short-term PFS (STPFS, PFS ≤ 3 months). Circulating cytokine levels were evaluated in paired peripheral blood samples collected before and after ICIs treatment.</p><p><strong>Results: </strong>Among 202 patients identified and 171 included (median follow-up: 41.0 months), 44 (25.7%) experienced LTPFS, associated with a 5-year overall survival (OS) rate of 81.2%. Squamous NSCLC, intermediate or poor lung immune prognostic index (LIPI) score, and liver metastases, were negatively associated with LTPFS. High tumor mutational burden (TMB, ≥ 10 mutations/megabase) was enriched in LTPFS compared to STPFS (P = 0.002). Patients with both high TMB and PD-L1 demonstrated the greatest survival benefit from first-line ICIs monotherapy (median PFS: 24.5 months, median OS: 67.0 months). Thirty-eight peripheral blood samples were collected before and after ICIs treatment from 10 patients with LTPFS and 9 with STPFS, which revealed increased CCL11 (P = 0.013) and decreased IL1RA (P = 0.001) and IL17A (P = 0.003) levels in LTPFS after ICIs treatment.</p><p><strong>Conclusion: </strong>Distinct clinical characteristics, including TMB, PD-L1, pathologic subtypes, LIPI score, number of organs involved, metastatic sites, and dynamic circulating cytokines profile features, can distinguish NSCLC patients achieving LTPFS from those with STPFS following first-line ICIs monotherapy.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"173"},"PeriodicalIF":4.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Durable response to nivolumab in combination with regional hyperthermia in a patient with PD-L1-negative metastatic head and neck squamous cell carcinoma. nivolumab联合局部热疗治疗pd - l1阴性转移性头颈部鳞状细胞癌患者的持久疗效
IF 4.6 2区 医学
Cancer Immunology, Immunotherapy Pub Date : 2025-04-17 DOI: 10.1007/s00262-025-04029-9
Luc M Berclaz, Anton Burkhard-Meier, Axel Lechner, Michael Völkl, Sinan E Güler, Sultan Abdel-Rahman, Sina Mansoorian, Wolfgang G Kunz, Thomas Knösel, Martin Canis, Michael von Bergwelt-Baildon, Rolf D Issels, Dorit Di Gioia, Lars H Lindner
{"title":"Durable response to nivolumab in combination with regional hyperthermia in a patient with PD-L1-negative metastatic head and neck squamous cell carcinoma.","authors":"Luc M Berclaz, Anton Burkhard-Meier, Axel Lechner, Michael Völkl, Sinan E Güler, Sultan Abdel-Rahman, Sina Mansoorian, Wolfgang G Kunz, Thomas Knösel, Martin Canis, Michael von Bergwelt-Baildon, Rolf D Issels, Dorit Di Gioia, Lars H Lindner","doi":"10.1007/s00262-025-04029-9","DOIUrl":"10.1007/s00262-025-04029-9","url":null,"abstract":"<p><p>We report a long-lasting response to the immune checkpoint inhibitor nivolumab in combination with regional hyperthermia (RHT) in a patient with recurrent metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) and negative programmed death ligand 1 (PD-L1) expression. Treatment was well tolerated with no local side effects. Tumor-related symptoms in the orbital and masticator area gradually decreased under treatment with nivolumab and RHT. Over the course of treatment, magnetic resonance imaging (MRI) showed a local tumor control in the heated tumor areas, while metastatic lesions developed in areas outside of the RHT field. This is the first case report demonstrating the feasibility and clinical potential of the addition of RHT in this patient collective with poor outcomes and low response rates to immune checkpoint inhibitors. RHT might be an additional tool to activate an immunogenic milieu responsive to immune checkpoint inhibitors.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 6","pages":"174"},"PeriodicalIF":4.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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