Journal of Hematology & Oncology最新文献

{"title":"CAR-NK cell therapy: latest updates from the 2024 ASH annual meeting","authors":"Ran Kong, Bingyu Liu, Hua Wang, Tiange Lu, Xiangxiang Zhou","doi":"10.1186/s13045-025-01677-3","DOIUrl":"https://doi.org/10.1186/s13045-025-01677-3","url":null,"abstract":"Natural killer cells, integral to the innate immune response, exhibit the inherent capacity to identify and eliminate cancer cells without prior exposure, positioning them as prime candidates for immunotherapeutic strategies. Chimeric antigen receptor-engineered natural killer (CAR-NK) cells obviate the requirement for human leukocyte antigen compatibility, simplifying personalized schedules and facilitating the manufacture of off-the-shelf products. In addition, CAR-NK cell therapy possesses lower risk of cytokine release syndrome and neurotoxicity, benefitting patients with higher security. Nevertheless, CAR-NK cell therapy is also confronted with challenges, including but not limited to short lifespan and restrictions from tumor microenvironment. Here, we summarized the latest advancements in the preclinical investigations and clinical trials of CAR-NK cell therapy from the 2024 ASH Annual Meeting.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"34 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells","authors":"Le Qin, Yunxin Lai, Ruocong Zhao, Xinru Wei, Jianyu Weng, Peilong Lai, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Qiubin Liang, Yangqiu Li, Xuchao Zhang, Yilong Wu, Pentao Liu, Yao Yao, Duanqing Pei, Xin Du, Peng Li","doi":"10.1186/s13045-025-01672-8","DOIUrl":"https://doi.org/10.1186/s13045-025-01672-8","url":null,"abstract":"<p><b>Correction: Journal of Hematology & Oncology (2017) 10:68 </b><b>https://doi.org/10.1186/s13045-017-0437-8</b></p><p>The authors wish to note the following:</p><p>In Supplemental Figure 1, the flow cytometry data that represent the transfection efficiencies of Meso.28z T cells on Day 12 and Day 15 were mistakenly duplicated. Both panels display a percentage of 34.9%, but upon reviewing our raw data, we found that the correct transfection efficiency for Day 15 should be 34.4%, not 34.9%. This discrepancy was caused by an error in copying and pasting during data preparation.</p><p>We confirm that this correction does not impact the overall conclusions or interpretation of the results presented in the article. To address this mistake, we kindly request the opportunity to replace the original Supplemental Figure 1 with a revised figure that accurately reflects the values. The original and revised Supplementary Figure 1 can be viewed via this Correction article.</p><span>Author notes</span><ol><li><p>Le Qin and Yunxin Lai are equal contributors.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China</p><p>Le Qin, Yunxin Lai, Ruocong Zhao, Xinru Wei, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Yao Yao, Duanqing Pei & Peng Li</p></li><li><p>Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China</p><p>Le Qin, Yunxin Lai, Ruocong Zhao, Xinru Wei, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Yao Yao, Duanqing Pei & Peng Li</p></li><li><p>State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China</p><p>Le Qin, Yunxin Lai, Ruocong Zhao, Xinru Wei, Baiheng Li, Simiao Lin, Suna Wang, Qiting Wu, Yao Yao & Peng Li</p></li><li><p>Department of Hematology, Guangdong General Hospital/Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, China</p><p>Jianyu Weng, Peilong Lai & Xin Du</p></li><li><p>InVivo Biomedicine Co. Ltd, Guangzhou, 510000, China</p><p>Qiubin Liang</p></li><li><p>Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China</p><p>Yangqiu Li</p></li><li><p>Guangdong Lung Cancer Institute, Medical Research Center, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China</p><p>Xuchao Zhang & Yilong Wu</p></li><li><p>Wellcome Trust Sanger Institute, Hinxton, Cambridge, England, CB10 1HH, UK</p><p>Pentao Liu</p></li></ol><span>Authors</span><ol><li><span>Le Qin</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Sch","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"49 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noncoding RNA-encoded peptides in cancer: biological functions, posttranslational modifications and therapeutic potential","authors":"Shiming Tan, Wenjuan Yang, Zongyao Ren, Qiu Peng, Xuemeng Xu, Xianjie Jiang, Zhu Wu, Linda Oyang, Xia Luo, Jinguan Lin, Longzheng Xia, Mingjing Peng, Nayiyuan Wu, Yanyan Tang, Yaqian Han, Qianjin Liao, Yujuan Zhou","doi":"10.1186/s13045-025-01671-9","DOIUrl":"https://doi.org/10.1186/s13045-025-01671-9","url":null,"abstract":"In the present era, noncoding RNAs (ncRNAs) have become a subject of considerable scientific interest, with peptides encoded by ncRNAs representing a particularly promising avenue of investigation. The identification of ncRNA-encoded peptides in human cancers is increasing. These peptides regulate cancer progression through multiple molecular mechanisms. Here, we delineate the patterns of diverse ncRNA-encoded peptides and provide a synopsis of the methodologies employed for the identification of ncRNAs that possess the capacity to encode these peptides. Furthermore, we discuss the impacts of ncRNA-encoded peptides on the biological behavior of cancer cells and the underlying molecular mechanisms. In conclusion, we describe the prospects of ncRNA-encoded peptides in cancer and the challenges that need to be overcome.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"64 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-15: from discovery to FDA approval","authors":"Zihai Li, John Wrangle, Kai He, Jonathan Sprent, Mark P. Rubinstein","doi":"10.1186/s13045-025-01664-8","DOIUrl":"https://doi.org/10.1186/s13045-025-01664-8","url":null,"abstract":"<p>In April 2024, the FDA approved the interleukin (IL)−15 superagonist, N-803 (Anktiva, nogapendekin alfa inbakicept-pmln), for the treatment of bladder cancer [1]. This is the first cytokine in over 30 years to receive FDA approval for the treatment of cancer, and the culmination of years of preclinical and clinical studies involving both academic- and industry- driven research.</p><p>To understand the steps leading to this landmark approval, it is helpful to review some key historical events (Fig. 1). Notably, the first cytokines FDA approved for the treatment of cancer were interferon (type 1) (1986, hairy cell leukemia) and IL-2 (1992, renal cell carcinoma) [2]. Within a few years of their initial approvals, both cytokines would also receive other FDA approvals including for the treatment of metastatic melanoma. While both cytokines have broad immune stimulatory activities, IL-2 is unique in that it is also a powerful lymphocyte growth factor [3,4,5,6]. These qualities led to the evaluation and use of IL-2 with many other experimental immunotherapies including adoptive cell therapy. Notably, the adoptive transfer of tumor infiltrating lymphocytes (TIL) in combination with IL-2 first showed efficacy in human patients in the late 1980s [7]. After decades of work, in February 2024, TIL (lifileucel) in combination with IL-2 received FDA approval for the treatment of melanoma [8], which is the first approved adoptive cell therapy using lymphocytes for the treatment of a solid tumor.</p><figure><figcaption><b data-test=\"figure-caption-text\">Fig. 1</b></figcaption><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13045-025-01664-8/MediaObjects/13045_2025_1664_Fig1_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"170\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13045-025-01664-8/MediaObjects/13045_2025_1664_Fig1_HTML.png\" width=\"685\"/></picture><p>Timeline of key events related to the discovery and development of IL-15 and BCG as therapeutics</p><span>Full size image</span><svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></figure><p>Despite its established efficacy, IL-2 has a short half-life, and at approved doses, IL-2 can induce life threatening toxicities [9]. This side effect profile likely severely curtailed subsequent clinical development. Thus, high dose IL-2 as a monotherapy was FDA approved for renal cell carcinoma and metastatic melanoma, clinical development for other indications halted despite evidence of efficacy in other cancers [10]. Thus began the effort to develop alternatives with a similar mechanism of action.</p><p>The discovery of IL-15 in 1994 was the first step in the development of a promising alternative to IL-2 [4,5,6, 11,12,13]. Like IL-2, IL-15 is a powerful ","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"12 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer vaccines: current status and future directions","authors":"Yingqiong Zhou, Yuquan Wei, Xiaohe Tian, Xiawei Wei","doi":"10.1186/s13045-025-01670-w","DOIUrl":"https://doi.org/10.1186/s13045-025-01670-w","url":null,"abstract":"Cancer continues to be a major global health burden, with high morbidity and mortality. Building on the success of immune checkpoint inhibitors and adoptive cellular therapy, cancer vaccines have garnered significant interest, but their clinical success remains modest. Benefiting from advancements in technology, many meticulously designed cancer vaccines have shown promise, warranting further investigations to reach their full potential. Cancer vaccines hold unique benefits, particularly for patients resistant to other therapies, and they offer the ability to initiate broad and durable T cell responses. In this review, we highlight the antigen selection for cancer vaccines, introduce the immune responses induced by vaccines, and propose strategies to enhance vaccine immunogenicity. Furthermore, we summarize key features and notable clinical advances of various vaccine platforms. Lastly, we delve into the mechanisms of tumor resistance and explore the potential benefits of combining cancer vaccines with standard treatments and other immunomodulatory approaches to improve vaccine efficacy.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"1 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-in-human evaluation of memory-like NK cells with an IL-15 super-agonist and CTLA-4 blockade in advanced head and neck cancer.","authors":"Roman M Shapiro, Michal Sheffer, Matthew A Booker, Michael Y Tolstorukov, Grace C Birch, Moshe Sade-Feldman, Jacy Fang, Shuqiang Li, Wesley Lu, Michela Ansuinelli, Remy Dulery, Mubin Tarannum, Joanna Baginska, Nishant Dwivedi, Ashish Kothari, Livius Penter, Yasmin Z Abdulhamid, Isabel E Kaplan, Dinh Khanhlinh, Ravindra Uppaluri, Robert A Redd, Sarah Nikiforow, John Koreth, Jerome Ritz, Catherine J Wu, Robert J Soiffer, Glenn J Hanna, Rizwan Romee","doi":"10.1186/s13045-025-01669-3","DOIUrl":"10.1186/s13045-025-01669-3","url":null,"abstract":"<p><strong>Background: </strong>Cytokine induced memory-like natural killer (CIML NK) cells combined with an IL-15 super-agonist (N-803) are a novel modality to treat relapsed/refractory head and neck cancer.</p><p><strong>Methods: </strong>We report data from a phase I trial of haploidentical CIML NK cells combined with N-803 with or without ipilimumab (IPI) in relapsed/refractory head and neck cancer patients after a median of 6 prior lines of therapy. The trial adhered to a 3 + 3 dose de-escalation design, with primary endpoint being safety. High-resolution immunophenotypic and transcriptional profiling characterized the NK cells and their interacting partners in vivo.</p><p><strong>Results: </strong>The primary safety endpoint was established, with dose-limiting toxicity in 1/10 patients. A transient disease control rate correlated with donor NK cell expansion, the latter occurring irrespective of IPI. The combination of CIML NK cells with N-803 and IPI was associated with increased early NK cell proliferation, contraction of Treg: Tcon, rapid recovery of recipient CD8⁺ T cells, and subsequent accelerated rejection of donor NK cells.</p><p><strong>Conclusions: </strong>CIML NK cells combined with N-803 and ipilimumab to treat head and neck cancer is safe, and associated with a more proliferative NK cell phenotype. However, the combination leads to reduced HLA mismatched NK cell persistence, resulting in an important limitation affecting NK cell combination therapies in clinical trials. These results inform evaluation of CIML NK therapy for advanced malignancies, with considerations for combination with IPI.</p><p><strong>Trial registration: </strong>NCT04290546.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"18 1","pages":"17"},"PeriodicalIF":29.5,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological activity of OST-01, a natural product from baccharis coridifolia, on breast cancer cells","authors":"HyunJun Kang, Dinh Hoa Hoang, Melissa Valerio, Khyatiben Pathak, William Graff, Alexis LeVee, Jun Wu, Mark A. LaBarge, David Frankhouser, Russell C. Rockne, Patrick Pirrotte, Bin Zhang, Joanne Mortimer, Le Xuan Truong Nguyen, Guido Marcucci","doi":"10.1186/s13045-025-01668-4","DOIUrl":"https://doi.org/10.1186/s13045-025-01668-4","url":null,"abstract":"Natural products have long been a viable source of therapeutic agents, providing unique structures and mechanisms that may be beneficial for cancer treatment. Herein we first report on the anticancer activity OST-01, a natural product from Baccharis Coridifolia, on breast cancer cells, including triple-negative breast cancer (TNBC). OST-01 significantly inhibited cell proliferation and oncogenic activities of TNBC cells in vitro. OST-01 also markedly inhibited TNBC tumor growth in vivo, with > 50% reduction in tumor size compared to vehicle control treatment in different in vivo models, i.e., cell line-derived (CDX), patient-derived (PDX), and mammary fat pad xenografts. Mechanistically, OST-01 induces ferroptosis by downregulating LRP8-regulated selenoproteins, i.e., GPX4. A shift from a basal-mesenchymal to a luminal-epithelial state of breast cancer stem cells (BCSCs) as supported by the downregulation of stemness (e.g., CD44) and mesenchymal (e.g., FN1 and vimentin) markers, along with the upregulation of differentiation markers (e.g., CD24) and luminal-epithelial markers (e.g., CK19), was also observed.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"43 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-LAG-3 antibody LBL-007 plus anti-PD-1 antibody toripalimab in advanced nasopharyngeal carcinoma and other solid tumors: an open-label, multicenter, phase Ib/II trial","authors":"Gang Chen, Dong-Chen Sun, Yi Ba, Ya-Xiong Zhang, Ting Zhou, Yuan-Yuan Zhao, Hong-Yun Zhao, Wen-Feng Fang, Yan Huang, Zhen Wang, Chao Deng, De-Sheng Hu, Wei Wang, Jin-Guan Lin, Gui-Ling Li, Su-Xia Luo, Zhi-Chao Fu, Hai-Sheng Zhu, Hui-Li Wang, Sheng-Li Cai, Xiao-Qiang Kang, Li Zhang, Yun-Peng Yang","doi":"10.1186/s13045-025-01666-6","DOIUrl":"https://doi.org/10.1186/s13045-025-01666-6","url":null,"abstract":"Open-label phase Ib/II study to investigate the safety and efficacy of LBL-007, an anti-LAG-3 antibody, plus toripalimab, an anti-PD-1 antibody, in patients with previously treated advanced nasopharyngeal carcinoma (NPC) and other solid tumors. Patients with advanced tumors refractory to prior standard therapies were enrolled. In phase Ib, patients received LBL-007 200 mg or 400 mg and toripalimab 240 mg intravenously once every 3 weeks. In phase II, all patients received LBL-007 at the recommended phase II dose (RP2D) and toripalimab 240 mg intravenously once every 3 weeks. The primary end points were safety in phase Ib and objective response rate (ORR) in phase II. The exploratory end point was the predictive capability of LAG-3 and PD-L1 expression for efficacy. Between November 30, 2021, and December 1, 2023, 80 patients were enrolled, including 30 (37.5%) with NPC and 50 (62.5%) with other tumors. Median follow-up was 26.0 months. In Phase Ib, LBL-007 was administered at 200 mg to four patients and 400 mg to six patients, with no dose-limiting toxicities observed. Therefore, the 400 mg dose of LBL-007 was established as the RP2D and administered to 70 patients in phase II. Nine (11.3%) of 80 patients had grade 3 or 4 treatment-related adverse events, the most common of which included anemia (2.5%), hyponatremia (2.5%), increased alanine aminotransferase (2.5%), increased aspartate aminotransferase (1.3%), and fatigue (1.3%). Eight patients (10.0%) had treatment-related serious adverse events. No treatment-related deaths were reported. In immunotherapy-naive NPC patients (n = 12), ORR was 33.3%, disease control rate (DCR) was 75%, and median progression-free survival (PFS) was 10.8 months (95% CI, 1.3 to not estimated). In IO-treated NPC patients (n = 17), ORR was 11.8%, DCR was 64.7%, and median PFS was 2.7 months (95% CI, 1.4 to 4.9). For other tumors, ORRs were 15.8% in immunotherapy-naive patients and 3.7% in immunotherapy-treated patients. Patients with ≥ 2 + LAG-3 expression had a higher ORR of 28.0%, compared to 7.7% in those with < 2 + LAG-3 expression. LBL-007 plus toripalimab exhibited a manageable safety profile in patients with advanced solid tumors and demonstrated promising antitumor activity in NPC, especially in immunotherapy-naive patients. These findings warrant further validation in future studies.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"48 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional regulatory network analysis identifies GRN as a key regulator bridging chemotherapy and immunotherapy response in small cell lung cancer","authors":"Seungyeul Yoo, Ayushi S. Patel, Sarah Karam, Yi Zhong, Li Wang, Feng Jiang, Ranran Kong, Sharon Bikvan, Wenhui Wang, Abhilasha Sinha, Charles A. Powell, Jun Zhu, Hideo Watanabe","doi":"10.1186/s13045-025-01667-5","DOIUrl":"https://doi.org/10.1186/s13045-025-01667-5","url":null,"abstract":"Small cell lung cancer (SCLC) is an aggressive and heterogeneous subtype, representing 15% of lung cancer cases. Although SCLC initially responds to etoposide and platinum (EP) chemotherapy, nearly all patients relapse with resistant tumors. While recent advances in immunotherapy have shown promise, only 10–20% of patients benefit, and effective stratification methods are lacking. The mechanisms of resistance to both therapeutics remain obscure. In this study, we aimed to gain insights into those leveraging a recent surge in the field of SCLC genomics. We constructed a regulatory network for SCLC and identified granulin precursor (GRN) as a hub of EP response associated genes. GRN-low patients showed improved survival with chemotherapy, while GRN-high patients exhibited resistance. GRN overexpression in SCLC cells conferred resistance to EP treatment and suppressed neuroendocrine features. GRN and its associated genes were linked to cancer cell intrinsic immunogenicity, and single-cell RNA-seq data revealed that GRN expression is particularly high in subsets of tumor-associated macrophages. In concordance with these findings, GRN-low tumors showed significantly better survival with chemo-immunotherapy, while GRN-high tumors did not benefit from additional immunotherapy. GRN-high tumors, associated with non-neuroendocrine (non-NE) subtypes, had a higher level of macrophage infiltration, potentially contributing to immunotherapy resistance. These results highlight GRN as a critical regulator of chemo-resistance and a potential biomarker for immunotherapy resistance in SCLC. Targeted therapeutic strategies for GRN-low patients could improve outcomes, while new approaches are needed for GRN-high patients. Overall, our findings implicate GRN as a bridge between chemotherapy and immunotherapy resistance through GRN-mediated mechanisms.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"28 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143125349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Prognostic impact of donor mitochondrial genomic variants in myelodysplastic neoplasms after stem-cell transplantation","authors":"Jing Dong, Shahram Arsang-Jang, Tao Zhang, Zhongyuan Chen, Yung-Tsi Bolon, Stephen Spellman, Raul Urrutia, Paul Auer, Wael Saber","doi":"10.1186/s13045-025-01662-w","DOIUrl":"https://doi.org/10.1186/s13045-025-01662-w","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Correction: Journal of Hematology &amp; Oncology (2024) 17:104&lt;/b&gt; &lt;b&gt;https://doi.org/10.1186/s13045-024-01622-w&lt;/b&gt;&lt;/p&gt;&lt;p&gt;The authors wish to note the following amendments to the affiliations and the funding in the original article.&lt;/p&gt;&lt;br/&gt;&lt;p&gt;The affiliations should instead be as follows:&lt;/p&gt;&lt;p&gt;• Wael Saber:&lt;/p&gt;&lt;br/&gt;&lt;p&gt;CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI&lt;/p&gt;&lt;p&gt;• Paul Auer:&lt;/p&gt;&lt;br/&gt;&lt;p&gt;Division of Biostatistics, Data Science Institute, Medical College of Wisconsin, Milwaukee, WI&lt;/p&gt;&lt;br/&gt;&lt;p&gt;CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI&lt;/p&gt;&lt;br/&gt;&lt;p&gt;Cancer Center Biostatistics Shared Resource, Medical College of Wisconsin, Milwaukee, WI&lt;/p&gt;&lt;p&gt;• Zhongyuan Chen:&lt;/p&gt;&lt;br/&gt;&lt;p&gt;Division of Biostatistics, Data Science Institute, Medical College of Wisconsin, Milwaukee, WI&lt;/p&gt;&lt;br/&gt;&lt;p&gt;CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI&lt;/p&gt;&lt;br/&gt;&lt;p&gt;The Funding should instead read as follows:&lt;/p&gt;&lt;p&gt;Jing Dong is supported by the NHLBI (K01 HL164972) and the Medical College of Wisconsin Cancer Center. N00014-17-1-2850 from the Office of Naval Research. CIBMTR is supported primarily by the Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); 75R60222C00011 from the Health Resources and Services Administration (HRSA); and N00014-23-1-2057 and N00014-24-1-2057 from the Office of Naval Research. Support is also provided by the Medical College of Wisconsin, NMDP, Gateway for Cancer Research, Pediatric Transplantation and Cellular Therapy Consortium and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies Corporation; ADC Therapeutics; Adienne SA; Alexion; AlloVir, Inc.; Amgen, Inc.; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics; BeiGene; BioLineRX; Blue Spark Technologies; bluebird bio, inc.; Blueprint Medicines; Bristol Myers Squibb Co.; CareDx Inc.; CSL Behring; CytoSen Therapeutics, Inc.; DKMS; Elevance Health; Eurofins Viracor, DBA Eurofins Transplant Diagnostics; Gamida-Cell, Ltd.; Gift of Life Biologics; Gift of Life Marrow Registry; GlaxoSmithKline; HistoGenetics; Incyte Corporation; Iovance; Janssen Research &amp; Development, LLC; Janssen/Johnson &amp; Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Karius; Kashi Clinical Laboratories; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Labcorp; Legend Biotech; Mallinckrodt Pharmaceuticals; Med Learning Group; Medac GmbH; Merck &amp; Co.; Mesoblast; Millennium, the Takeda Oncology Co.; Miller Pharmacal Group, Inc.; Miltenyi Biotec, Inc.; MorphoSys; MSA-EDITLife; Neovii Pharmaceuticals AG; Novartis Pharmaceuticals Corporation; Omeros Corporation; OptumHealth; Orca Biosystems, In","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"61 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}