Jacc: Cardiooncology最新文献

英文中文

Cardiac Troponin Screening and Clinical Outcomes in Patients Receiving Immunotherapy 接受免疫治疗患者的心肌肌钙蛋白筛查和临床结果。

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2025-10-01 DOI: 10.1016/j.jaccao.2025.06.009

Evaline Cheng MD , Maja Ivanovic MD , Antonia Chan MD , Sidra Xu , Miguel Franquiz PharmD, MD , Carissa Lee BS , Jonathan You MD , Muhammad Fazal MD , Yann Le Guen PhD , Ryan Batchelder PA-C , Sunil A. Reddy MD , Tamiko Katsumoto MD , Kavitha Ramchandran MD , A. Dimitrios Colevas MD , Saad Kahn MD , Alice Fan MD , Heather Wakelee MD , Paul Cheng MD, PhD , Eldrin F. Lewis MD, MPH , Sean M. Wu MD, PhD , Han Zhu MD

Background

Immune checkpoint inhibitors (ICIs) are associated with cardiotoxicities such as myocarditis. However, data on the implementation and outcomes of cardiac biomarker screening remain limited.

Objectives

The aim of this study was to examine the impact of cardiac troponin I (cTnI) surveillance integrated with symptom-based triaging in patients receiving immunotherapy.

Methods

A single-center retrospective cohort study was conducted among adults who underwent routine serial cTnI monitoring during immunotherapy between January 2019 and October 2021. For patients with elevated cTnI, clinical presentation, management, and outcomes were analyzed. Major adverse cardiac events included arrhythmia, myocarditis, heart failure, acute coronary syndrome, stroke, and pericardial effusion. Patients were followed for 24 months from their first ICI dose.

Results

Among 428 patients (mean age 67.1 ± 13.9 years, 60.3% men), 42 (9.8%) had elevated cTnI detected through monitoring. Compared with symptomatic patients, asymptomatic patients more often underwent outpatient evaluation (88.0% vs 17.6%; P < 0.001) and continued immunotherapy (68.0% vs 35.3%; P < 0.001), whereas symptomatic patients more often underwent myocarditis-specific diagnostics such as cardiac magnetic resonance imaging (58.8% vs 8.0%; P = 0.001) and received immunosuppression (47.1% vs 8.0%; P = 0.008). The cumulative incidence of major adverse cardiac events at 1.5 years following cTnI elevation was 19.0% (95% CI: 7.0%-31.1%) and was significantly higher in symptomatic vs asymptomatic patients (subdistribution HR: 18.9; 95% CI: 2.2-162.5; P = 0.008). Symptomatic patients had a significantly higher risk for all-cause mortality at 2-year follow-up (HR: 3.24; 95% CI: 1.06-9.94; P = 0.04). In total, 6 patients were diagnosed with myocarditis, with no cardiac-related deaths.

Conclusions

cTnI surveillance integrated with symptom-based triaging can facilitate early intervention and treatment of cardiotoxicities such as myocarditis.

背景：免疫检查点抑制剂（ICIs）与心肌炎等心脏毒性有关。然而，关于心脏生物标志物筛查的实施和结果的数据仍然有限。目的：本研究的目的是检查心脏肌钙蛋白I （cTnI）监测与基于症状的分诊对接受免疫治疗的患者的影响。方法：对2019年1月至2021年10月在免疫治疗期间接受常规连续cTnI监测的成年人进行单中心回顾性队列研究。对于cTnI升高的患者，分析了临床表现、管理和结果。主要的心脏不良事件包括心律失常、心肌炎、心力衰竭、急性冠状动脉综合征、中风和心包积液。患者从第一次服用ICI开始随访24个月。结果：428例患者（平均年龄67.1±13.9岁，男性60.3%）中，42例（9.8%）监测到cTnI升高。与有症状患者相比，无症状患者更常接受门诊评估(88.0% vs 17.6%；P < 0.001)和继续免疫治疗(68.0% vs 35.3%；P < 0.001)，而有症状的患者更常接受心肌炎特异性诊断，如心脏磁共振成像(58.8% vs 8.0%；P = 0.001)，接受免疫抑制(47.1% vs 8.0%；P = 0.008)。cTnI升高后1.5年主要不良心脏事件的累积发生率为19.0% (95% CI: 7.0%-31.1%)，有症状患者比无症状患者显著更高(亚分布HR: 18.9；95% ci: 2.2-162.5；P = 0.008)。在2年随访中，有症状患者的全因死亡风险显著增高(HR: 3.24；95% ci: 1.06-9.94；P = 0.04)。总共有6例患者被诊断为心肌炎，无心脏相关死亡。结论：cTnI监测结合基于症状的分诊可以促进心肌炎等心脏毒性的早期干预和治疗。

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引用次数: 0

Recognizing and Responding to Cardiac Risk With Osimertinib 使用奥西替尼识别和应对心脏风险。

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2025-10-01 DOI: 10.1016/j.jaccao.2025.08.002

Eun Kyoung Kim MD, PhD , Se-Hoon Lee MD, PhD

引用次数: 0

Anthracycline Dose, Myocardial Injury, and Change in Left Ventricular Function in the Cardiac CARE Trial 心脏CARE试验中蒽环类药物剂量、心肌损伤和左心室功能改变。

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2025-10-01 DOI: 10.1016/j.jaccao.2025.06.003

Krithika Loganath MBBS ∗ , Kuan Ken Lee PhD ∗ , Olga Oikonomidou MD, BSc, MSc, MRes, PhD , Peter Hall PhD , Nicholas L. Mills BSc Hons, MBChB, PhD , Shruti Joshi PhD , Trisha Singh PhD , Tom McGillivray PhD , Scott Semple PhD , Ninian N. Lang BSc (Hons), MB ChB, PhD , Marc R. Dweck BSc (Hons), MBChB, PhD , Peter A. Henriksen BSc, MB ChB, PhD

Background

Anthracycline-induced toxicity contributes to long-term cardiovascular morbidity in cancer survivors. Cardiac troponin is recommended for risk stratification and diagnosis, but the relationship between troponin concentrations—particularly those measured using high-sensitivity assays—and subsequent cardiac dysfunction remains unclear.

Objectives

The authors sought to examine associations between high-sensitivity cardiac troponin I (hs-cTnI), cumulative anthracycline dose, number of treatment cycles, and changes in left ventricular (LV) function.

Methods

The Cardiac CARE trial was a prospective, multicenter, randomized, open-label, blinded-endpoint study of cardioprotective therapy in patients with elevated baseline hs-cTnI undergoing high-dose anthracycline chemotherapy. Hs-cTnI was measured before each chemotherapy cycle and at 2, 4, and 6 months after treatment. LV function was assessed by cardiac magnetic resonance at baseline and 6 months post-chemotherapy.

Results

Of the 175 participants (mean age 52 ± 11 years; 86.5% women), 171 received ≥3 anthracycline cycles. The median cumulative epirubicin-equivalent dose was 600 mg/m² (Q1-Q3: 513-660 mg/m²). Peak hs-cTnI concentrations were observed 2 months after chemotherapy (median 14.0 ng/L [Q1-Q3: 9.0-30.5 ng/L]) and statistically correlated with the number of treatment cycles, but not with cumulative dose. No participants developed an LV ejection fraction (LVEF) <50%, although 24 of 171 patients (14.0%) experienced a decline in LVEF >10%. Hs-cTnI showed a weak correlation with LVEF change and was not predictive of global longitudinal strain by cardiac magnetic resonance.

Conclusions

Hs-cTnI levels were not associated with cumulative anthracycline dose and were only weakly associated with LVEF decline at 6 months. These findings suggest that mild myocardial injury, as reflected by hs-cTnI elevation, may not reliably predict subsequent cardiac dysfunction following anthracycline chemotherapy.

背景：蒽环类药物引起的毒性有助于癌症幸存者的长期心血管发病率。心肌肌钙蛋白被推荐用于风险分层和诊断，但是肌钙蛋白浓度（特别是那些使用高灵敏度测定法测量的）与随后的心功能障碍之间的关系尚不清楚。目的：作者试图研究高敏感性心肌肌钙蛋白I （hs-cTnI）、蒽环类药物累积剂量、治疗周期数和左心室（LV）功能变化之间的关系。方法：Cardiac CARE试验是一项前瞻性、多中心、随机、开放标签、盲终点的研究，对接受大剂量蒽环类药物化疗的基线hs-cTnI升高的患者进行心脏保护治疗。在每个化疗周期前和治疗后2、4和6个月测量Hs-cTnI。在基线和化疗后6个月通过心脏磁共振评估左室功能。结果：175名参与者(平均年龄52±11岁；86.5%女性)，171例接受≥3个蒽环类药物周期。中位累积表柔比星当量剂量为600 mg/m2 （Q1-Q3: 513-660 mg/m2）。化疗后2个月观察到hs-cTnI浓度峰值（中位数14.0 ng/L [Q1-Q3: 9.0-30.5 ng/L]），与治疗周期数有统计学相关性，但与累积剂量无关。没有参与者出现左室射血分数（LVEF） 10%。Hs-cTnI与LVEF变化呈弱相关，可预测心脏磁共振整体纵向应变。结论：Hs-cTnI水平与累积蒽环类药物剂量无关，仅与6个月时LVEF下降弱相关。这些发现表明，hs-cTnI升高所反映的轻度心肌损伤可能不能可靠地预测蒽环类药物化疗后的心功能障碍。

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引用次数: 0

Trastuzumab Cardiotoxicity 曲妥珠单抗心脏毒性：不需要射血分数监测没有先前的蒽环类药物暴露。

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2025-10-01 DOI: 10.1016/j.jaccao.2025.04.008

Maya Guglin MD, PhD

引用次数: 0

Risk of Heart Failure Hospitalization in Patients Treated With Osimertinib 奥西替尼治疗患者心力衰竭住院的风险：一项基于人群的回顾性队列研究

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2025-10-01 DOI: 10.1016/j.jaccao.2025.06.011

Yasuhisa Tatebe PhD, Yuta Tanaka PhD, Yohei Manabe BPharm, Shinobu Okano BPharm, Tsukasa Higashionna MS, Hirofumi Hamano PhD, Kiminaka Murakawa PhD, Yoshito Zamami PhD

Background

Osimertinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, is used to treat patients with epidermal growth factor receptor–mutant non–small-cell lung cancer. Although osimertinib has been linked to heart failure (HF), detailed risk estimates remain unclear.

Objectives

The aim of this study was to examine the association between osimertinib use and HF hospitalization.

Methods

In this retrospective cohort study using a large-scale Japanese claims database, patients diagnosed with lung cancer between April 2008 and December 2021 who received cancer therapy were identified. Patients were categorized into osimertinib and control groups according to treatment received. The incidence of HF hospitalization during the treatment period was compared between the groups. Multivariable analyses were performed before and after propensity score matching.

Results

The osimertinib and control groups included 11,391 and 108,144 patients, respectively. Among the entire cohort, the median age was 70 years (Q1-Q3: 64-76 years), and the median follow-up duration was 173 days (Q1-Q3: 73-448 days). The incidence of HF hospitalization was 9.9 and 4.1 cases per 1,000 person-years in the osimertinib and control groups, respectively. In multivariable analysis, osimertinib was associated with a higher risk for HF hospitalization than control therapy (subdistribution HR: 2.56; 95% CI: 2.07-3.18; P < 0.001). This association remained significant after propensity score matching (subdistribution HR: 2.29; 95% CI: 1.62-3.24; P < 0.001).

Conclusions

Osimertinib use was associated with an increased risk for HF hospitalization. Cardiac function should be closely monitored in patients receiving osimertinib.

背景：奥西替尼是一种口服表皮生长因子受体酪氨酸激酶抑制剂，用于治疗表皮生长因子受体突变的非小细胞肺癌。尽管奥西替尼与心力衰竭（HF）有关，但详细的风险评估仍不清楚。目的：本研究的目的是研究使用奥西替尼与心衰住院之间的关系。方法：在这项使用大规模日本索赔数据库的回顾性队列研究中，确定了2008年4月至2021年12月期间接受癌症治疗的肺癌患者。根据治疗情况将患者分为奥西替尼组和对照组。比较两组治疗期间HF住院发生率。在倾向评分匹配前后进行多变量分析。结果：奥西替尼组和对照组患者分别为11391例和108144例。整个队列中，中位年龄为70岁（Q1-Q3: 64-76岁），中位随访时间为173天（Q1-Q3: 73-448天）。在奥西替尼组和对照组中，HF住院率分别为9.9例/ 1000人年和4.1例/ 1000人年。在多变量分析中，与对照组相比，奥西替尼与较高的HF住院风险相关（亚分布HR: 2.56; 95% CI: 2.07-3.18; P < 0.001）。在倾向评分匹配后，这种关联仍然显著（亚分布HR: 2.29; 95% CI: 1.62-3.24; P < 0.001）。结论：使用奥西替尼与HF住院风险增加相关。接受奥西替尼治疗的患者应密切监测心功能。

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引用次数: 0

Bidirectional Interaction in Cardio-Oncology Toward Novel Therapeutic Strategies for Cardiovascular Diseases 双向相互作用的心脏肿瘤学对心血管疾病的新治疗策略：JACC：心脏肿瘤学入门。

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2025-08-01 DOI: 10.1016/j.jaccao.2025.04.007

Lama Awwad MSc, Laris Achlaug MSc, Sharon Aviram PhD, Ami Aronheim PhD

引用次数: 0

Reconsidering the Oncologic Implications of Antihypertensive Therapy 重新考虑抗高血压治疗的肿瘤学意义

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2025-08-01 DOI: 10.1016/j.jaccao.2025.05.015

Ioannis Skalidis MD, PhD, Henri Lu MD, Niccolo Maurizi MD, Georgios Tzimas MD, Panagiotis Antiochos MD

引用次数: 0

Cardiovascular Risk, Health Metrics, and Cancer Prediction 心血管风险、健康指标和癌症预测：范围综述。

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2025-08-01 DOI: 10.1016/j.jaccao.2025.05.011

Gretell Henriquez-Santos MD , Ji-Eun Kim PhD , Sant J. Kumar MD , Alicia A. Livinski MPH, MA , Jacqueline B. Vo PhD, RN, MPH , Fang Zhu PhD, MPH , Jungnam Joo PhD , Joseph J. Shearer PhD, MPH , Maryam Hashemian MD, PhD , Véronique L. Roger MD, MPH

Background

Cardiovascular disease (CVD) and cancer are leading global causes of morbidity and mortality. Given the shared risk factors, it is plausible that CVD risk scores and cardiovascular health (CVH) metrics could predict cancer risk.

Objectives

The authors sought to identify and summarize studies examining the association between CVD risk scores, CVH metrics, and incident cancer.

Methods

A systematic search of 4 databases (Embase, PubMed, Scopus, Web of Science: Core) was conducted in April 2024 without language or date restrictions. Five reviewers (G.H., J.K., S.J.K., M.H., V.L.R.) independently screened records using Covidence software and extracted data from eligible prospective studies (adults aged ≥18 years; cancer incidence as outcome; CVD risk scores or CVH metrics as exposure).

Results

Of 4,165 records screened, 13 studies (14 CVD or CVH metrics) were included. Heterogeneity between scales precluded a meta-analysis. Four studies evaluated CVD risk scores (eg, atherosclerotic CVD) and 10 reported CVH metrics (eg, the American Heart Association’s Life’s Simple 7). Sample sizes ranged from 1,880 to 342,226, with median follow-up from 8.1 to 29.6 years. The majority included all types of cancer (71.4%), including breast, lung, colorectal, and prostate cancer types, with cancer events ranging from 387 to 11,643. Higher CVD risk scores were consistently associated with increased cancer risk incidence (HRs: 1.16-3.71). Ideal CVH metrics were associated with reduced risk (HRs: 0.49-0.95).

Conclusions

Despite heterogeneity in CVD risk metrics and cancer types, most studies suggested that worse CVD risk scores or CVH metrics predict greater cancer risk. Future studies should focus on specific CVD risk metrics and cancer types to produce evidence suitable for a meta-analysis.

背景：心血管疾病（CVD）和癌症是全球发病率和死亡率的主要原因。考虑到共同的风险因素，心血管疾病风险评分和心血管健康（CVH）指标可以预测癌症风险是合理的。目的：作者试图识别和总结检验CVD风险评分、CVH指标和癌症发生率之间关系的研究。方法：于2024年4月对Embase、PubMed、Scopus、Web of Science: Core 4个数据库进行系统检索，无语言和日期限制。5位审稿人（g.h.、j.k.、s.j.k.、m.h.、V.L.R.）使用covid - ence软件独立筛选记录，并从符合条件的前瞻性研究中提取数据(成人≥18岁；癌症发病率作为结果；心血管疾病风险评分或CVH指标作为暴露)。结果：在筛选的4165份记录中，包括13项研究（14项CVD或CVH指标）。量表间的异质性妨碍了meta分析。4项研究评估了CVD风险评分（如动脉粥样硬化性CVD）， 10项研究报告了CVH指标（如美国心脏协会的Life's Simple 7）。样本量从1880年到342226年不等，中位随访从8.1年到29.6年不等。大多数包括所有类型的癌症（71.4%），包括乳腺癌、肺癌、结肠直肠癌和前列腺癌，癌症事件从387到11,643不等。心血管疾病风险评分越高，癌症风险发生率越高（hr: 1.16-3.71）。理想的CVH指标与风险降低相关（hr: 0.49-0.95）。结论：尽管心血管疾病风险指标和癌症类型存在异质性，但大多数研究表明，心血管疾病风险评分或CVH指标越差，患癌症的风险越高。未来的研究应侧重于特定的心血管疾病风险指标和癌症类型，以产生适合荟萃分析的证据。

{"title":"Cardiovascular Risk, Health Metrics, and Cancer Prediction","authors":"Gretell Henriquez-Santos MD , Ji-Eun Kim PhD , Sant J. Kumar MD , Alicia A. Livinski MPH, MA , Jacqueline B. Vo PhD, RN, MPH , Fang Zhu PhD, MPH , Jungnam Joo PhD , Joseph J. Shearer PhD, MPH , Maryam Hashemian MD, PhD , Véronique L. Roger MD, MPH","doi":"10.1016/j.jaccao.2025.05.011","DOIUrl":"10.1016/j.jaccao.2025.05.011","url":null,"abstract":"<div><h3>Background</h3><div>Cardiovascular disease (CVD) and cancer are leading global causes of morbidity and mortality. Given the shared risk factors, it is plausible that CVD risk scores and cardiovascular health (CVH) metrics could predict cancer risk.</div></div><div><h3>Objectives</h3><div>The authors sought to identify and summarize studies examining the association between CVD risk scores, CVH metrics, and incident cancer.</div></div><div><h3>Methods</h3><div>A systematic search of 4 databases (Embase, PubMed, Scopus, Web of Science: Core) was conducted in April 2024 without language or date restrictions. Five reviewers (G.H., J.K., S.J.K., M.H., V.L.R.) independently screened records using Covidence software and extracted data from eligible prospective studies (adults aged ≥18 years; cancer incidence as outcome; CVD risk scores or CVH metrics as exposure).</div></div><div><h3>Results</h3><div>Of 4,165 records screened, 13 studies (14 CVD or CVH metrics) were included. Heterogeneity between scales precluded a meta-analysis. Four studies evaluated CVD risk scores (eg, atherosclerotic CVD) and 10 reported CVH metrics (eg, the American Heart Association’s Life’s Simple 7). Sample sizes ranged from 1,880 to 342,226, with median follow-up from 8.1 to 29.6 years. The majority included all types of cancer (71.4%), including breast, lung, colorectal, and prostate cancer types, with cancer events ranging from 387 to 11,643. Higher CVD risk scores were consistently associated with increased cancer risk incidence (HRs: 1.16-3.71). Ideal CVH metrics were associated with reduced risk (HRs: 0.49-0.95).</div></div><div><h3>Conclusions</h3><div>Despite heterogeneity in CVD risk metrics and cancer types, most studies suggested that worse CVD risk scores or CVH metrics predict greater cancer risk. Future studies should focus on specific CVD risk metrics and cancer types to produce evidence suitable for a meta-analysis.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 5","pages":"Pages 593-606"},"PeriodicalIF":12.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643905","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}

引用次数: 0

Current Insights in Bidirectional Cardio-Oncology: Heart Failure Driving Cancer 双向心脏肿瘤学的最新见解：心力衰竭驱动癌症

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2025-08-01 DOI: 10.1016/j.jaccao.2025.05.014

Rudolf A. de Boer MD, PhD , Laura I. Yousif MSc , Joseph Pierre Aboumsallem PhD, Wouter C. Meijers MD, PhD

引用次数: 0

Ischemic Injury Drives Nascent Tumor Growth Via Accelerated Hematopoietic Aging 缺血损伤通过加速造血老化驱动新生肿瘤生长

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2025-08-01 DOI: 10.1016/j.jaccao.2025.06.005

Alexandra A.C. Newman PhD , José Gabriel Barcia Durán PhD , Richard Von Itter MPhil , Jessie M. Dalman BA , Brian Lim MD , Morgane Gourvest PhD , Tarik Zahr PhD , Kristin M. Wang MPhil , Tracy Zhang MS , Noah Albarracin BS , Whitney G. Rubin BS , Fazli K. Bozal PhD , Kory J. Lavine MD, PhD , Chiara Giannarelli MD, PhD , Michael Gildea PhD , Coen van Solingen PhD , Kathryn J. Moore PhD

Background

Patients with peripheral artery disease have an increased risk of cancer development. Aging-associated changes in hematopoietic stem and progenitor cells (HSPCs), including inflammation and increased myelopoiesis, are implicated in both cardiovascular disease and cancer, but their contributions to cardiovascular disease–driven tumor progression are unclear.

Objectives

This study sought to study tumor growth after peripheral ischemia and consequent changes within the HSPC bone marrow compartment to uncover mechanisms through which altered hematopoiesis promotes cancer.

Methods

Mammary cancer (E0771) growth was monitored in C57BL/6J mice after hind limb ischemia (HLI) or sham surgery. The tumor immune microenvironment, circulatory immune cells, and HSPC compartment were assessed by flow cytometry. Next-generation single-cell RNA and assay for transposase-accessible chromatin sequencing of bone marrow progenitors was performed to assess the distinct and synergistic transcriptomic and epigenetic changes of cancer and peripheral ischemia. The functional impact on tumor progression and persistence of ischemia-induced epigenetic reprogramming of HSPCs and their myeloid progeny was examined by bone marrow transplantation.

Results

Peripheral ischemia increased monocyte and neutrophil output at the expense of lymphocytes, driven by a shift toward CD150^hi myeloid-biased hematopoietic stem cells. This was associated with accelerated cancer growth and enrichment of tumors with myeloid cells (monocytes, macrophages, neutrophils) and regulatory T cells. Increased myelopoiesis was also supported by sequencing analyses showing HLI and tumor-induced transcriptional and epigenetic enrichment for inflammatory (NLRP3 inflammasome) and aging-associated neogenin-1, thrombospondin-1) signatures in subsets of monocyte/dendritic progenitors. HLI-accelerated tumor growth and myeloid-skewing was transmissible via bone marrow transplantation, indicating long-term reprogramming of innate immune responses.

Conclusions

Peripheral ischemia enhances inflammaging of hematopoietic stem cells and long-lasting alterations to antitumoral immunity, accelerating breast tumor growth.

外周动脉疾病患者患癌症的风险增加。造血干细胞和祖细胞（HSPCs）的衰老相关变化，包括炎症和骨髓生成增加，与心血管疾病和癌症都有关系，但它们对心血管疾病驱动的肿瘤进展的贡献尚不清楚。目的本研究旨在研究外周缺血后肿瘤的生长和HSPC骨髓腔室随之发生的变化，以揭示造血功能改变促进癌症的机制。方法观察C57BL/6J小鼠后肢缺血（HLI）或假手术后乳腺癌（E0771）的生长情况。流式细胞术检测肿瘤免疫微环境、循环免疫细胞、HSPC室。采用下一代单细胞RNA和转座酶可及的骨髓祖细胞染色质测序测定来评估癌症和外周缺血的独特和协同的转录组学和表观遗传变化。通过骨髓移植研究了缺血诱导的HSPCs及其髓系后代表观遗传重编程对肿瘤进展和持久性的功能影响。结果外周血缺血增加单核细胞和中性粒细胞的输出，以牺牲淋巴细胞为代价，由CD150hi骨髓偏向造血干细胞的转变驱动。这与肿瘤的加速生长和骨髓细胞（单核细胞、巨噬细胞、中性粒细胞）和调节性T细胞的富集有关。在单核细胞/树突状祖细胞亚群中，测序分析显示HLI和肿瘤诱导的炎症（NLRP3炎性体）和衰老相关的neogenin-1， thrombospontin -1)特征的转录和表观遗传富集也支持骨髓生成的增加。hli加速的肿瘤生长和骨髓歪斜通过骨髓移植传播，表明先天免疫反应的长期重编程。结论外周血缺血可增强造血干细胞的炎症反应和抗肿瘤免疫功能，促进乳腺肿瘤的生长。

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