Critical reviews in oncology/hematology最新文献_第7页

Clinical benefit of immune checkpoint inhibitors in elderly cancer patients: Current evidence from immunosenescence pathophysiology to clinical trial results

IF 5.5 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-01-30 DOI: 10.1016/j.critrevonc.2025.104635

Dimitrios C. Ziogas, Charalampos Theocharopoulos, Katerina Aravantinou, Aristeidis E. Boukouris, Dimitra Stefanou, Amalia Anastasopoulou, Panagiotis-Petros Lialios, George Lyrarakis, Helen Gogas

The age-related decline in immunity appears to be associated not only with cancer development but also with differential responses to immune checkpoint inhibitors (ICIs). Despite their increasing utility across various malignancies and therapeutic settings, limited data -derived primarily from subgroup analyses of randomized controlled trials (RCTs), pooled meta-analyses, and retrospective studies- are available on the effects of aging on their efficacy and toxicity. Immunosenescence, characterized by the progressive decline of the function of the immune system, and inflammaging, a state of persistent low-grade sterile inflammation, may influence ICI outcomes. Additionally, the incidence, severity, and subtypes of immune-related adverse events (irAEs) may differ between older and younger individuals due to loss of immunotolerance. In the current review, starting from a a comprehensive discussion of the pathophysiology of immunosenescence, we proceed to critically review age-related retrospective and randomized evidence supporting FDA-approved ICIs. We highlight similarities or differences across age groups and the clinical benefit of ICIs in elderly versus younger cancer patients. The optimal integration of ICIs in geriatric oncology necessitates greater inclusion of this patient demographic in RCTs along with real-world data in order to acquire robust data which will guide evidence-based treatment decisions for this population.

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引用次数: 0

Combining gut microbiota modulation and immunotherapy: A promising approach for treating microsatellite stable colorectal cancer

IF 5.5 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-01-27 DOI: 10.1016/j.critrevonc.2025.104629

Yujie Chang , Min Long , Hanguo Shan , Logen Liu , Shangwei Zhong , Jun-Li Luo

Colorectal cancer (CRC) is one of the most prevalent and lethal cancers worldwide, ranking third in incidence and second in mortality. While immunotherapy has shown promise in patients with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H), its effectiveness in proficient mismatch repair (pMMR) or microsatellite stable (MSS) CRC remains limited. Recent advances highlight the gut microbiota as a potential modulator of anti-tumor immunity. The gut microbiome can significantly influence the efficacy of immune checkpoint inhibitors (ICIs), especially in pMMR/MSS CRC, by modulating immune responses and systemic inflammation. This review explores the role of the gut microbiota in pMMR/MSS CRC, the mechanisms by which it may enhance immunotherapy, and current strategies for microbiota modulation. We discuss the potential benefits of combining microbiota-targeting interventions with immunotherapy to improve treatment outcomes for pMMR/MSS CRC patients.

引用次数: 0

Rhythm is essential: Unraveling the relation between the circadian clock and cancer

IF 5.5 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-01-27 DOI: 10.1016/j.critrevonc.2025.104632

Olajumoke Ogunlusi , Abantika Ghosh , Mrinmoy Sarkar , Kayla Carter , Harshini Davuluri , Mahul Chakraborty , Kristin Eckel-Mahan , Alex Keene , Jerome S. Menet , Deborah Bell-Pedersen , Tapasree Roy Sarkar

Physiological processes such as the sleep-wake cycle, metabolism, hormone secretion, neurotransmitter release, sensory capabilities, and a variety of behaviors, including sleep, are controlled by a circadian rhythm adapted to 24-hour day-night periodicity. Disruption of circadian rhythm may lead to the risks of numerous diseases, including cancers. Several epidemiological and clinical data reveal a connection between the disruption of circadian rhythms and cancer. On the contrary, oncogenic processes may suppress the homeostatic balance imposed by the circadian clock. The integration of circadian biology into cancer research offers new options for making cancer treatment more effective, and the pharmacological modulation of core clock genes is a new approach in cancer therapy. This review highlights the role of the circadian clock in tumorigenesis, how clock disruption alters the tumor microenvironment, and discusses how pharmacological modulation of circadian clock genes can lead to new therapeutic options.

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引用次数: 0

Optimization of immunotherapy-based combinations for metastatic renal cell carcinoma: A network meta-analysis

IF 5.5 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-01-27 DOI: 10.1016/j.critrevonc.2025.104630

Sohyeon Park, Kalynn Park, Chaeyoon Kim, Sandy Jeong Rhie

Background

Despite numerous meta-analyses comparing the efficacy and safety of immunotherapy-based combination therapies, the optimal therapeutic combinations remain unclear. This study aims to evaluate the optimal application of all immunotherapy-based combination therapy for advanced/metastatic renal cell carcinoma, focusing on efficacy and safety.

Methods

We systemically searched the Web of Science, Cochrane Library, and PubMed for studies regarding the first-line immunotherapy-based combination therapy in patients with advanced or metastatic renal cell carcinoma until April 15, 2024. We used network meta-analysis using a random effect model to facilitate direct and indirect treatment comparisons across outcomes.

Results

Seven clinical studies, including 5542 patients with metastatic renal cell carcinoma, were included in the network meta-analysis analysis. Regarding progression-free survival and overall survival, combined Toripalimab + Axitinib significantly outperformed other immunotherapy-based combination therapies. This regimen significantly improved progression-free survival in the intermediate/poor risk group when stratified by prognosis prediction risks compared to sunitinib alone. For the objective response rate, Avelumab + Axitinib was the most preferred strategy in the favorable-risk group, while Nivolumab + Cabozantinib was favored in the intermediate/poor-risk group compared to other immunotherapy-based combinations. The combinations of Nivolumab + Ipilimumab and Atezolizumab + Bevacizumab had favorable safety profiles.

Conclusions

Immunotherapy-based combination therapies significantly improved progression-free survival, overall survival and objective response rate in patients with metastatic renal cell carcinoma compared to sunitinib monotherapy. However, careful monitoring and personalized treatment strategies are required to balance efficacy and safety in patients with underlying conditions. Future research should focus on optimizing treatment protocols and elucidating the mechanisms of adverse events.

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引用次数: 0

Cellular senescence in tumor immune escape: Mechanisms, implications, and therapeutic potential

IF 5.5 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-01-24 DOI: 10.1016/j.critrevonc.2025.104628

Li You , Qinghua Wu

Cellular senescence, a hallmark of aging, has emerged as a captivating area of research in tumor immunology with profound implications for cancer prevention and treatment. In the tumor microenvironment, senescent cells exhibit a dual role, simultaneously hindering tumor development through collaboration with immune cells and evading immune cell attacks by upregulating immunoinhibitory proteins. However, the intricate immune escape mechanism of cellular senescence in the tumor microenvironment remains a subject of intense investigation. Chronic inflammation is exacerbated by cellular senescence through the upregulation of pro-inflammatory factors such as interleukin-1β, thereby augmenting the risk of tumorigenesis. Additionally, the interplay between autophagy and cellular senescence adds another layer of complexity. Autophagy, known to slow down the aging process by reducing p53/p21 levels, may be downregulated by cellular senescence. To harness the therapeutic potential of cellular senescence, targeting its immunological aspects has gained significant attention. Strategies such as immune checkpoint inhibitors and T-cell senescence inhibition are being explored in the context of cellular senescence immunotherapy. In this comprehensive review, we provide a compelling overview of the regulation of cellular senescence and delve into the influencing factors, including chronic inflammation, autophagy, and circadian rhythms, associated with senescence in the tumor microenvironment. We specifically focus on unraveling the enigmatic dual role of cellular senescence in tumor immune escape. By deciphering the intricate nature of cellular senescence in the tumor microenvironment, this review aims to advance our understanding and pave the way for leveraging senescence as a promising target for tumor immunotherapy applications.

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引用次数: 0

Future directions in the evaluation and management of newly diagnosed metastatic cancer

IF 5.5 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-01-24 DOI: 10.1016/j.critrevonc.2025.104631

Eric J. Lehrer , Chachrit Khunsriraksakul , Sara Garrett , Daniel M. Trifiletti , Jason P. Sheehan , Matthias Guckenberger , Alexander V. Louie , Shankar Siva , Piet Ost , Karyn A. Goodman , Laura A. Dawson , Leila T. Tchelebi , Jonathan T. Yang , Timothy N. Showalter , Henry S. Park , Daniel E. Spratt , Amar U. Kishan , Gaorav P. Gupta , Chirag Shah , Stefano Fanti , Nicholas G. Zaorsky

There is much debate regarding optimal selection in patients with metastatic cancer who should undergo local treatment (surgery or radiation treatment) to the primary tumor and/or metastases. Additionally, the optimal treatment of newly diagnosed metastatic cancer is largely unclear. Current prognostication systems to best inform these clinical scenarios are limited, as all metastatic patients are grouped together as having Stage IV disease without further incorporation of patient and disease-specific covariates that significantly impact patient outcomes. Therefore, improving current prognostic scoring systems and incorporation of these covariates is essential to best individualize treatment for patients with metastatic cancer. In this narrative review article, we provide a detailed review of prognostication systems that can be used for both the site of metastasis and primary site to best tailor treatment in these patients. Additionally, we discuss the incorporation and ongoing developments in radiographic, genomic, and biostatistical techniques that can be used as prognostication tools.

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引用次数: 0

Small cell lung cancer unveiled: Exploring the untapped resource of circulating tumor cells-derived organoids 揭示小细胞肺癌：探索循环肿瘤细胞衍生类器官的未开发资源。

IF 5.5 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-01-19 DOI: 10.1016/j.critrevonc.2025.104622

Jesús A. Pérez-Cabello , Ana Artero-Castro , Sonia Molina-Pinelo

Small cell lung cancer (SCLC) remains a challenge in oncology due to its aggressive behavior and dismal prognosis. Despite advances in treatments, novel strategies are urgently needed. Enter liquid biopsy—a game-changer in SCLC management. This revolutionary non-invasive approach allows for the analysis of circulating tumor cells (CTCs), offering insights into tumor behavior and treatment responses. Our review focuses on a groundbreaking frontier: harnessing CTCs to create three-dimensional (3D) organoid models. These models, derived from CTCs that break away from the primary tumor or metastatic locations, hold immense potential for revolutionizing cancer research, especially in SCLC. We explore the essential conditions for successfully establishing CTC-derived organoids—a transformative approach with profound implications for personalized medicine. Our evaluation spans diverse isolation techniques, shedding light on their advantages and limitations. Furthermore, we uncover the critical factors governing the cultivation of 3D organoids from CTCs, meticulously mimicking the tumor microenvironment. This review comprehensively elucidates the molecular characterization of these organoids, showcasing their potential in identifying treatment targets and predicting responses. In essence, our review amalgamates cutting-edge methodologies for isolating CTCs, establishing transformative CTC-derived organoids, and characterizing their molecular landscape. This represents a promising frontier for advancing personalized medicine in the complex realm of SCLC management and holds significant implications for translational research.

小细胞肺癌（SCLC）由于其侵袭性行为和预后不佳，在肿瘤学中仍然是一个挑战。尽管在治疗方面取得了进展，但迫切需要新的策略。液体活检的出现改变了SCLC的管理。这种革命性的非侵入性方法允许对循环肿瘤细胞（ctc）进行分析，提供对肿瘤行为和治疗反应的见解。我们的综述集中在一个开创性的前沿：利用ctc来创建三维（3D）类器官模型。这些模型来源于脱离原发肿瘤或转移部位的ctc，具有巨大的癌症研究革命潜力，特别是在SCLC中。我们探索成功建立ctc衍生类器官的基本条件-一种对个性化医疗具有深远影响的变革性方法。我们的评估涵盖了不同的隔离技术，揭示了它们的优点和局限性。此外，我们揭示了控制ctc培养3D类器官的关键因素，精心模拟肿瘤微环境。这篇综述全面阐述了这些类器官的分子特征，展示了它们在识别治疗靶点和预测反应方面的潜力。从本质上讲，我们的综述融合了分离ctc，建立变革性ctc衍生类器官和表征其分子景观的尖端方法。这代表了在复杂的SCLC管理领域推进个性化医疗的一个有希望的前沿，并对转化研究具有重要意义。

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引用次数: 0

« Augmented radiotherapy » in the management of high-risk prostate cancer (PCa): A systematic review “增强放疗”在高危前列腺癌（PCa）治疗中的应用：一项系统综述。

IF 5.5 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-01-18 DOI: 10.1016/j.critrevonc.2025.104623

Jennifer Le Guévelou , Vedang Murthy , Thomas Zilli , Luca Nicosia , Alberto Bossi , Leonard P. Bokhorst , Eric Barret , Idir Ouzaid , Paul L. Nguyen , Federica Ferrario , Cyrus Chargari , Stefano Arcangeli , Nicolas Magne , Paul Sargos

Background

In patients with high-risk (HR) prostate cancer (PCa) treated with radiotherapy and androgen deprivation therapy (ADT), intensification with androgen receptor pathway inhibitor (ARPI) improves overall survival (OS), at the cost of significant side-effects. We hypothesized that “augmented RT” schedules (defined as either dose-escalation on the prostate gland over 78 Gy and/or addition of whole pelvic radiotherapy (WPRT)), combined with long-term ADT can reach excellent prostate cancer specific survival (PCSS) in this population with little detrimental impact on quality of life.

Methods

We searched Pubmed database until February 8, 2024. Studies reporting both oncological and toxicity outcomes after “augmented RT” were deemed eligible. Studies without ADT or with ARPI intensification were deemed ineligible.

Results

Dose-escalation within the prostate gland at doses over 78 Gy halved the risk of biochemical recurrence at 5 years, with however no impact on PCSS. The addition of WPRT provides a 5-year disease-free survival (DFS) reaching 89.5 % at 5 years, with no significant increase in late grade≥ 2 genito-urinary (GU) or gastrointestinal (GI) toxicity. Combined approaches result in 9-year PCSS ranging between 96.1 % and 100 %. Most approaches demonstrated excellent safety profiles.

Conclusions

“Augmented RT” reached excellent oncological outcomes, with minimal additional toxicity. The development of biomarkers might lead to further treatment personalization, in the rapidly evolving landscape of systemic therapies.

背景：在接受放疗和雄激素剥夺治疗（ADT）的高危（HR）前列腺癌（PCa）患者中，雄激素受体途径抑制剂（ARPI）的强化治疗可提高总生存率（OS），但代价是显著的副作用。我们假设“增强放疗”计划（定义为前列腺剂量增加超过78Gy和/或增加全盆腔放疗（WPRT）），结合长期ADT可以在该人群中达到极好的前列腺癌特异性生存率（PCSS），对生活质量几乎没有不利影响。方法：检索Pubmed数据库至2024年2月8日。报告“增强型放射治疗”后肿瘤和毒性结果的研究被认为是合格的。没有ADT或ARPI增强的研究被认为不合格。结果：前列腺内剂量增加，剂量超过78Gy， 5年生化复发风险减半，但对PCSS没有影响。WPRT的加入使5年无病生存率（DFS）达到89.5%，晚期≥2级泌尿生殖系统（GU）或胃肠道（GI）毒性没有显著增加。综合方法的9年PCSS范围在96.1%至100%之间。大多数方法显示出良好的安全性。结论：“增强型放射治疗”达到了极好的肿瘤学结果，并且具有最小的额外毒性。在快速发展的全身治疗领域，生物标志物的发展可能会导致进一步的治疗个性化。

{"title":"« Augmented radiotherapy » in the management of high-risk prostate cancer (PCa): A systematic review","authors":"Jennifer Le Guévelou , Vedang Murthy , Thomas Zilli , Luca Nicosia , Alberto Bossi , Leonard P. Bokhorst , Eric Barret , Idir Ouzaid , Paul L. Nguyen , Federica Ferrario , Cyrus Chargari , Stefano Arcangeli , Nicolas Magne , Paul Sargos","doi":"10.1016/j.critrevonc.2025.104623","DOIUrl":"10.1016/j.critrevonc.2025.104623","url":null,"abstract":"<div><h3>Background</h3><div>In patients with high-risk (HR) prostate cancer (PCa) treated with radiotherapy and androgen deprivation therapy (ADT), intensification with androgen receptor pathway inhibitor (ARPI) improves overall survival (OS), at the cost of significant side-effects. We hypothesized that “augmented RT” schedules (defined as either dose-escalation on the prostate gland over 78 Gy and/or addition of whole pelvic radiotherapy (WPRT)), combined with long-term ADT can reach excellent prostate cancer specific survival (PCSS) in this population with little detrimental impact on quality of life.</div></div><div><h3>Methods</h3><div>We searched Pubmed database until February 8, 2024. Studies reporting both oncological and toxicity outcomes after “augmented RT” were deemed eligible. Studies without ADT or with ARPI intensification were deemed ineligible.</div></div><div><h3>Results</h3><div>Dose-escalation within the prostate gland at doses over 78 Gy halved the risk of biochemical recurrence at 5 years, with however no impact on PCSS. The addition of WPRT provides a 5-year disease-free survival (DFS) reaching 89.5 % at 5 years, with no significant increase in late grade≥ 2 genito-urinary (GU) or gastrointestinal (GI) toxicity. Combined approaches result in 9-year PCSS ranging between 96.1 % and 100 %. Most approaches demonstrated excellent safety profiles.</div></div><div><h3>Conclusions</h3><div>“Augmented RT” reached excellent oncological outcomes, with minimal additional toxicity. The development of biomarkers might lead to further treatment personalization, in the rapidly evolving landscape of systemic therapies.</div></div>","PeriodicalId":11358,"journal":{"name":"Critical reviews in oncology/hematology","volume":"207 ","pages":"Article 104623"},"PeriodicalIF":5.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Real-world evidence in extensive disease small cell lung cancer: The missing piece of the puzzle 广泛疾病小细胞肺癌的真实证据：拼图缺失的那一块。

IF 5.5 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-01-17 DOI: 10.1016/j.critrevonc.2025.104618

Paola Damiano , Alessio Stefani , Alice Avancini , Lorenzo Belluomini , Emilio Bria , Sara Pilotto

Small cell lung cancer (SCLC) is a highly aggressive disease, often diagnosed at an advanced stage and with limited treatment options. In recent years, immunotherapy has been approved in combination with chemotherapy in the first line setting of extensive stage disease (ES-SCLC). However, only 10–15 % of patients with ES-SCLC treated with chemoimmunotherapy (CT-IO) experience a long-term benefit. In addition, patients are often clinically frail due to advanced age, comorbidities, and disease-related symptoms, making SCLC a challenging condition. Real-world evidence (RWE) becomes particularly valuable in this scenario, not only to confirm the results of pivotal trials, but also to evaluate the outcomes of CT-IO in populations that are generally excluded from clinical trials. RWE could also define the role of integrative treatments such as thoracic consolidation radiotherapy and prophylactic cranial irradiation, which are used in selected patients in the clinical practice but were scarcely applied in pivotal trials. In this review, we focused on RWE in ES-SCLC, with the aim of improving clinical decision making. Notably, real-world data have largely confirmed the efficacy and safety of CT-IO observed in pivotal clinical trials, with a possible benefit even in more fragile patients. However, these studies also highlight that a significant proportion of the ES-SCLC population remains untreated due to poor clinical conditions.

小细胞肺癌（SCLC）是一种高度侵袭性的疾病，通常在晚期诊断出来，治疗选择有限。近年来，免疫治疗已被批准与化疗联合用于广泛分期疾病（ES-SCLC）的一线治疗。然而，只有10-15%的ES-SCLC患者接受了化学免疫疗法（CT-IO）的长期获益。此外，由于高龄、合并症和疾病相关症状，患者通常在临床上虚弱，使SCLC成为一种具有挑战性的疾病。在这种情况下，真实世界证据（RWE）变得特别有价值，不仅可以证实关键试验的结果，还可以评估通常被排除在临床试验之外的人群的CT-IO结果。RWE还可以确定综合治疗的作用，如胸部巩固放疗和预防性颅脑照射，这些治疗在临床实践中用于选定的患者，但很少用于关键试验。在这篇综述中，我们关注ES-SCLC的RWE，目的是改善临床决策。值得注意的是，现实世界的数据在很大程度上证实了关键临床试验中观察到的CT-IO的有效性和安全性，甚至在更脆弱的患者中也可能受益。然而，这些研究也强调，由于临床条件差，很大一部分ES-SCLC患者仍未得到治疗。

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引用次数: 0

Fibrinogen: A new player and target on the formation of pre-metastatic niche in tumor metastasis 纤维蛋白原：肿瘤转移前生态位形成的新参与者和靶点。

IF 5.5 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-01-16 DOI: 10.1016/j.critrevonc.2025.104625

Yuxin Zhang , Zelin Li , Jiamao Zhang , Tatenda Mafa , Jingyu Zhang , Hui Zhu , Lifang Chen , Zhen Zong , Lingling Yang

Tumor metastasis involves a series of complex and coordinated processes, which is the main cause of patient death and still a significant challenge in cancer treatment. Pre-metastatic niches (PMN), a specialized microenvironment that develops in distant organs prior to the arrival of metastatic cancer cells, plays a crucial role in driving tumor metastasis. The development of PMN depends on a complex series of cellular and molecular components including tumor-derived factors, bone marrow-derived cells, resident immune cells, and extracellular matrix. Fibrinogen, a key factor in the typical blood clotting process, is related to tumor metastasis and prognosis, according to a growing body of evidence in recent years. Fibrinogen has emerged as an important factor in mediating the formation of tumor microenvironment. Nevertheless, a clear and detailed mechanism by which fibrinogen promotes tumor metastasis remains unknown. In this review, we first explore the roles of fibrinogen in the development of PMN from four perspectives: immunosuppression, inflammation, angiogenesis, and extracellular matrix remodeling. We highlight the significance of fibrinogen in shaping PMN and discuss its potential therapeutic values, opening new avenues for targeting fibrinogen to prevent or treat metastasis.

肿瘤转移涉及一系列复杂而协调的过程，是导致患者死亡的主要原因，也是癌症治疗的一个重大挑战。转移前生态位（Pre-metastatic niche， PMN）是一种特异性的微环境，在肿瘤转移过程中起着至关重要的作用。PMN的发展取决于一系列复杂的细胞和分子成分，包括肿瘤源性因子、骨髓源性细胞、常驻免疫细胞和细胞外基质。近年来越来越多的证据表明，纤维蛋白原是典型凝血过程中的关键因子，与肿瘤转移和预后有关。纤维蛋白原已成为介导肿瘤微环境形成的重要因素。然而，纤维蛋白原促进肿瘤转移的具体机制尚不清楚。在本文中，我们首先从免疫抑制、炎症、血管生成和细胞外基质重塑四个方面探讨纤维蛋白原在PMN发生中的作用。我们强调纤维蛋白原在PMN形成中的重要性，并讨论其潜在的治疗价值，为靶向纤维蛋白原预防或治疗转移开辟了新的途径。

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引用次数: 0