Critical reviews in oncology/hematology最新文献

{"title":"Bystander effect in antibody-drug conjugates: navigating the fine line in tumor heterogeneity.","authors":"Yiming Wang, Xi Cheng, Xuan Li, Weijia Chen, Xiaotao Zhang, Yanhao Liu","doi":"10.1016/j.critrevonc.2025.104979","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2025.104979","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) represent a transformative advancement in targeted cancer therapy by combining monoclonal antibodies with cytotoxic payloads. A critical yet underexplored feature of ADCs is the bystander effect, wherein released payloads diffuse into neighboring cells regardless of target antigen expression. This review synthesizes current understanding of the mechanisms, clinical implications, and optimization strategies related to this phenomenon. Mechanistically, cleavable linkers, hydrophobic payloads, and internalization are critical for bystander activity. However, the characteristics of the tumor microenvironment-elevated interstitial fluid pressure, binding site barrier (BSB), and hypoxia-restrict ADC penetration. Clinically, ADCs with bystander effects (e.g., trastuzumab deruxtecan), demonstrate superior efficacy compared to non-bystander ADCs (e.g., trastuzumab emtansine). Despite these advantages, bystander effect raises concerns regarding off-target toxicity and variable efficacy depending on antigen expression. For instance, while the bystander effect allows payloads to penetrate BSB and increase the killing range, non-bystander ADCs like ARX788 may offer comparable efficacy with reduced toxicity in homogeneous settings. Current insights highlight the need to balance bystander potency with target specificity, particularly in tumors with low antigen density or heterogeneous spatial distribution. Future research should focus on three key areas: (1) quantifying bystander contributions in vivo; (2) clarifying spatiotemporal regulation of payload diffusion by TME factors such as hypoxia and binding-site barriers; and (3) validating combinatorial strategies, including Fc engineering, internalization induction, and TME remodeling, to maximize therapeutic indices. Bridging these gaps will refine ADC design paradigms, aligning with precision oncology's goal of optimizing efficacy while minimizing systemic toxicity.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"104979"},"PeriodicalIF":5.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145254077","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":"Adjuvant Immunotherapy in High-Risk Renal Cell Carcinoma: Indications, Limitations, and Perspectives. A Consensus Statement from the GIOTTO Uro-Oncology Group.","authors":"Giandomenico Roviello, Federico Paolieri, Martina Catalano, Luca Galli, Laura Doni, Federico Peschiera, Alessandro Pili, Michele Sisani, Bloise Francesco","doi":"10.1016/j.critrevonc.2025.104978","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2025.104978","url":null,"abstract":"<p><p>Renal cell carcinoma (RCC) is often diagnosed at a localized stage and treated with surgery. However, up to 40% of patients may experience recurrence despite complete resection. The introduction of immune checkpoint inhibitors, particularly pembrolizumab, has changed the adjuvant treatment landscape. The Tuscan Interdisciplinary Uro-Oncological Group (GIOTTO) provides practical guidance on patient selection and clinical use of adjuvant pembrolizumab in RCC.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"104978"},"PeriodicalIF":5.6,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246126","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":"Immune checkpoint inhibitor-related thrombocytopenia: Current status and future perspectives.","authors":"Peng-Fei Zhang, Xiao-Cui Ye, Xuan-Qiong Shi, Ling-Xuan Fu, Zhi-Han Yang","doi":"10.1016/j.critrevonc.2025.104976","DOIUrl":"10.1016/j.critrevonc.2025.104976","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have achieved significant success in cancer treatment, yet their associated adverse effects, particularly ICI-related thrombocytopenia (irTCP), are gaining increasing attention. IrTCP leads to serious complications, which affect treatment outcomes and quality of life. Clinical manifestations of irTCP may vary from mild to severe, necessitating careful monitoring during ICIs therapy. To date, several immune-mediated mechanisms, including the destruction of platelets and bone marrow suppression, have been revealed to play crucial roles in the pathogenesis of irTCP. Despite advancements in understanding these mechanisms, challenges remain in the timely diagnosis and effective management of irTCP. In this review, we synthesize the latest findings in the field and elucidate the mechanisms, clinical manifestations, diagnostic approaches, and management strategies of irTCP, aiming to provide insights for clinical practice and future research directions.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"104976"},"PeriodicalIF":5.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228564","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":"Recent advances in nanoparticles with a PD-L1-based therapy combination of chemotherapy for lung cancer.","authors":"Abdulkareem Shareef, Hayder Naji Sameer, Ahmed Yaseen, Zainab H Athab, Mohaned Adil, Omer Qutaiba B Allela","doi":"10.1016/j.critrevonc.2025.104872","DOIUrl":"10.1016/j.critrevonc.2025.104872","url":null,"abstract":"<p><p>Globally, lung cancer (LC) continues to be the primary cause of cancer-related fatalities. The clinical use of immune checkpoint inhibitors (ICIs) in the treatment of small cell lung cancer (SCLC) follows significantly behind that of non-small cell lung cancer (NSCLC). In advanced NSCLC, combining chemotherapy (CHT) with PD-L1 inhibitors has increased overall survival (OS) and progression-free survival, especially in patients with high PD-L1 expression. Additionally, a new standard of therapy for extensive-stage SCLC has been authorized for atezolizumab in combination with carboplatin and etoposide. However, the combination of PD-L1 inhibitors plus CHT raises the risk of toxicities associated with CHT as well as immune-related side effects such as hepatitis, colitis, and pneumonitis. To minimize side effects, using nanoparticles (NPs) for medication delivery in immunochemotherapy for LC is crucial. In preclinical applications, NPs with transport and/or immunomodulation capabilities have been effectively integrated with ICT. Delivery NPs safeguard and regulate the intended release of their cargo. Generally speaking, we have examined the various ICHT-based LC treatment options in this research. The types of NPs available to mitigate the limitations of this treatment for LC have been studied. Lastly, we covered the clinical constraints and strategies to reduce them. This review article combines evidence from a wide range of sources, including PubMed/NCBI, Google Scholar, and ClinicalTrials.gov, all published within the last few years.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"104872"},"PeriodicalIF":5.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786150","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":"Gut microbiota and chemoradiotherapy response in rectal cancer: Biomarker opportunities.","authors":"Christophe Taoum, Amandine Devaux, Philippe Rouanet, Pierre-Emmanuel Colombo, Delphine Boucher, Mathilde Bonnet","doi":"10.1016/j.critrevonc.2025.104974","DOIUrl":"10.1016/j.critrevonc.2025.104974","url":null,"abstract":"<p><p>The gut microbiota is increasingly recognized as a key factor in rectal carcinogenesis. This review synthesizes current clinical and preclinical evidence linking specific microbial signatures, such as Fusobacterium nucleatum, Duodenibacillus massiliensis and colibactin-producing Escherichia coli (CoPEC) to chemoradiotherapy (CRT) treatment efficacy and resistance. Microbiota-driven mechanisms include immune modulation, inflammation, and drug metabolism. We highlight emerging microbial biomarkers and therapeutic strategies such as antibiotics, probiotics, and fecal microbiota transplantation. Integrating microbiome profiling into clinical workflows could refine patient stratification and enhance CRT efficacy in rectal cancer. Ongoing clinical trials aim to validate these associations and establish robust microbial biomarkers for CRT response prediction in rectal cancer.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"104974"},"PeriodicalIF":5.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214601","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":"From Innate Power to Intelligent Design: The Evolution of NK Cell-Based Cancer Immunotherapy.","authors":"Israth Jahan Tuhin, Hong Jia Zhu, Masuma Akter Monty, Jin Wen Tan, Nan Xu, Jing Ye, Lei Yu","doi":"10.1016/j.critrevonc.2025.104972","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2025.104972","url":null,"abstract":"<p><p>Natural killer (NK) cells have emerged as a promising platform for cancer immunotherapy due to their intrinsic cytotoxicity, lack of antigen restriction, and minimal risk of graft-versus-host disease, enabling the development of safe and scalable \"off-the-shelf\" therapies. However, their clinical efficacy, particularly in solid tumors, remains limited by poor in vivo persistence, inadequate tumor infiltration, and suppression by the immunosuppressive tumor microenvironment (TME). This review highlights the recent advances in genetic engineering strategies to enhance NK cell antitumor function. We discuss the optimization of chimeric antigen receptors (CARs) specifically for NK cells, the integration of immune checkpoint resistance, metabolic reprogramming, and the incorporation of cytokine support to improve survival and potency. In parallel, we explore combination strategies that synergize with NK cells, including monoclonal antibodies, oncolytic viruses, vaccines, and adoptive immune cell therapy. Additionally, we examine innovative platforms such as nanoparticle delivery systems and NK cell-derived exosomes to further enhance therapeutic outcomes. By systematically addressing the intrinsic and extrinsic limitations of NK cells through genetic precision and combinatorial immunomodulation, NK-based therapies are poised to transition from supportive to frontline modalities in cancer treatment. This review provides a comprehensive roadmap for the next generation of NK cell therapies with broad translational potential.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"104972"},"PeriodicalIF":5.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208229","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":"Erratum to \"Beyond the blood-brain barrier: Intranasal vaccines in cancer immunotherapy\" [Crit. Rev. Oncol./Hematol. 216C (2025) 104938].","authors":"Anju James, P S Vajrashree, G S Meghana, K Trideva Sastri, A R Akhila, Chinamyee U Gowda, V Balamuralidhara","doi":"10.1016/j.critrevonc.2025.104966","DOIUrl":"https://doi.org/10.1016/j.critrevonc.2025.104966","url":null,"abstract":"","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"104966"},"PeriodicalIF":5.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180849","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":"Mesenchymal stem cell infusion to accelerate hematopoietic recovery after transplantation: A comprehensive systematic review of clinical studies (2000-2025).","authors":"Noushin Pouryazdanpanah, Vahid Moazed, Roohollah Mirzaee Khalilabadi, Tania Dehesh, Alireza Farsinejad","doi":"10.1016/j.critrevonc.2025.104875","DOIUrl":"10.1016/j.critrevonc.2025.104875","url":null,"abstract":"<p><strong>Background: </strong>Hematopoietic stem cell transplantation (HSCT) is a standard therapy for various hematologic diseases, yet delayed engraftment remains a significant challenge. Mesenchymal stem cells (MSCs) have attracted attention for their potential to enhance hematopoietic recovery due to their immunomodulatory and supportive functions. This systematic review aimed to evaluate the clinical impact of MSC infusion on engraftment outcomes after HSCT.</p><p><strong>Method: </strong>We systematically searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library for clinical studies published between 2000 and 2025. Eligible studies included randomized trials, cohort studies, and case series that assessed MSCs for improving engraftment. Data were synthesized qualitatively.</p><p><strong>Result: </strong>Forty-seven studies involving 1777 patients were included. MSCs were primarily derived from bone marrow or umbilical cord and administered intravenously. Approximately 79 % of the studies reported enhanced engraftment, with particular benefit for platelet recovery. The average neutrophil and platelet engraftment times in MSC recipients were 13.96 and 21.61 days, respectively. No serious adverse events related to MSC infusion were reported.</p><p><strong>Conclusion: </strong>Current clinical evidence supports the safety and potential efficacy of MSCs in promoting hematopoietic engraftment, especially platelet recovery, in HSCT recipients. Further high-quality randomized trials are required to confirm these findings. This systematic review is registered in PROSPERO (CRD420251082387).</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"104875"},"PeriodicalIF":5.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805438","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":"Fatty acid in the tumor microenvironment: Perspectives for immunotherapy.","authors":"Ting Li, Yi-Ran Bie, Shan-Mei Chen, Yao Shang, Pei-Shan Hu","doi":"10.1016/j.critrevonc.2025.104878","DOIUrl":"10.1016/j.critrevonc.2025.104878","url":null,"abstract":"<p><p>Fatty acids (FA) are essential macromolecules in living organisms and play critical roles in processes such as cancer development, inflammation, and autoimmunity. Immune responses and metabolic changes are involved in tumor occurrence, development, invasion, and metastasis, and therapies targeting immunity and metabolism have gradually begun to be developed in clinical practice. Recent studies have revealed alterations in fatty acid metabolism in tumor microenvironment, suggesting that the modulation of fatty acid metabolism can affect the efficacy of immunotherapy. In this review, we summarize the effects of fatty acids on cancer immunotherapy in aspects including tumor cell metabolism, protein lipid modification, and clinical applications. A deeper understanding of the mechanisms by which FA and their metabolites participate in immune response can enhance our knowledge of their function in tumor development and their impact on the immune system, thereby providing new strategies for improving cancer immunotherapy.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"104878"},"PeriodicalIF":5.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144801233","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":"PD-1/PD-L1 inhibitors in advanced, unresectable esophageal squamous-cell carcinoma: A meta-analysis of their effects across patient subgroups.","authors":"Mohammed S Beshr, Rana H Shembesh, Abdelaziz H Salama, Imane Chenfouh, Sarah M Alfaqaih, Abdallah Khashan, Arwi Omar Kara, Maram Abuajamieh, Eman Basheer, Zahraa Alla Ansaf, Esraa Arhaym, Mohamedhen Vall Nounou, Mohamed E Ali, Elizabeth C Smyth, Muhammed Elhadi, Markus Moehler","doi":"10.1016/j.critrevonc.2025.104876","DOIUrl":"10.1016/j.critrevonc.2025.104876","url":null,"abstract":"<p><strong>Background: </strong>Advanced esophageal cell carcinoma (ESCC) is associated with poor survival outcomes. PD-1/PD-L1 inhibitors have been approved for the treatment of advanced ESCC. We aim to study PD-1/PD-L1 inhibitors across other variables in advanced ESCC, including data presented at the September 2024 FDA Oncologic Drugs Advisory Committee (ODAC) meeting.</p><p><strong>Methods: </strong>On February 28, 2025, we conducted a comprehensive search using PubMed, Web of Science, Scopus, and the Cochrane Library to identify randomized clinical trials evaluating PD-1/PD-L1 inhibitors in advanced ESCC. The primary endpoints were overall survival (OS) and progression-free survival (PFS). Subgroup analyses were performed based on the following variables: age, gender, smoking status, ECOG performance status, liver metastasis, disease stage (locally advanced vs. metastatic), combined positive score (CPS; particularly with cutoff values of CPS 5 and CPS 1-9), and tumor area positivity (TAP). Effect sizes were estimated using the hazard ratio (HR) with random effects model.</p><p><strong>Results: </strong>Out of 5514 articles screened, only 13 papers were included, involving 6672 patients. PD-1/PD-L1 inhibitors significantly improved OS in both first- and second-line. In the first-line setting (combined with chemotherapy), they reduced the risk of death by 32 % (HR: 0.68; 95 % CI: 0.63-0.74, p < 0.001), while in the second-line setting (used as monotherapy), they reduced mortality by 27 % (HR: 0.73; 95 % CI: 0.66-0.81, p < 0.001). For PFS, a significant benefit was seen only in first-line treatment (HR: 0.62; 95 % CI: 0.58-0.67, p < 0.001) but not in second-line (HR: 0.89; 95 % CI: 0.76-1.04, p = 0.128), with a significant difference between treatment lines (p < 0.001). Most subgroups in our study demonstrated significant survival benefits, except for current smokers (HR: 0.58; 95 % CI: 0.31-1.09; p = 0.089). Finally, all CPS subgroups showed survival benefits in the first-line setting except those with CPS < 1 (PD-L1 negative). A similar pattern was observed in the second-line setting.</p><p><strong>Conclusions: </strong>PD-1/PD-L1 inhibitors significantly improve OS over chemotherapy in both first- and second-line advanced ESCC. PFS improved only in the first line. More effective therapies for the second line are still needed. Current smokers showed no survival benefit, unlike former or never smokers. OS benefit was absent in PD-L1-negative patients (CPS <1) and greatest in those with CPS ≥ 10.</p>","PeriodicalId":93958,"journal":{"name":"Critical reviews in oncology/hematology","volume":" ","pages":"104876"},"PeriodicalIF":5.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796339","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}