Risk Factors, Incidence, and Prognosis of Thromboembolism in Cancer Patients Treated With Immune Checkpoint Inhibitors

Zou, Xue-lin; Chen, Wei-yong; Zhang, Guangyan; Ke, Hua Zhu; Yang, Qiuhong; Li, Xiaobo

doi:10.3389/fphar.2021.747075

Cited by 5 publications

(3 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MDSCs can promote platelet aggregation. Also, through CXCR1/MDSCs, induce tumor to release Neutrophil Extracellular Traps (NETs) which play a significant role in thrombosis [84].…”

Section: The Role Of Platelets In Immunity Inflammation and Iraesmentioning

confidence: 99%

The Potential Role of Circulating Inflammatory Cells in Predicting the Safety, Efficacy and Immune-related Adverse Events of Immune Check-point Inhibitors: A Narrative Review

K Rugambwa

2023

GMR

View full text Add to dashboard Cite

Immune checkpoint blockade has influenced the course of cancer treatment with improved Overall Survival (OS) and durable responses in many malignancies. Despite these responses, their mechanism of action has brought different set of adverse events that are severe and life-threatening in a subset of patients. Moreover, not all patients have shown to benefit from this treatment although their tumors express U.S. Federal and Drug Administration (FDA) approved biomarkers i.e programmed cell Death Protein 1 (PD-1) and its ligand (PD-L1), Microsatellite Instability (MSI) and Tumor Mutation Burden (TMB). Limitations of these markers has stimulated further research to identify and incorporate other markers that could serve as an adjunct to the current approved ones. Circulating inflammatory cells are among biomarkers that have shown to have a prognostic and predictive value in determining treatment response to Immune Checkpoint Inhibitors (ICI) and risk of Immune-Related Adverse Events (irAEs). This review aims to provide more details on the key inflammatory cells that play a pivotal role in cancer progression and inhibition and how their interaction in the tumor micro-environment (TME) affects response to immune checkpoint blockade and predicting irAEs. Moreover examples of prognostic models that have incorporated these cells will be highlighted.

show abstract

“…MDSCs can promote platelet aggregation. Also, through CXCR1/MDSCs, induce tumor to release Neutrophil Extracellular Traps (NETs) which play a significant role in thrombosis [84].…”

Section: The Role Of Platelets In Immunity Inflammation and Iraesmentioning

confidence: 99%

The Potential Role of Circulating Inflammatory Cells in Predicting the Safety, Efficacy and Immune-related Adverse Events of Immune Check-point Inhibitors: A Narrative Review

K Rugambwa

2023

GMR

View full text Add to dashboard Cite

show abstract

“…In the current study, we observed a trend toward a higher lethality rate of venous embolism and thrombosis when ICIs and VEGFIs were used together compared with their individual use. The mechanisms involved in the increased frequency of thromboembolism with ICIs remain unclear but include increased tissue factor production in monocytes associated with T-cell activation (Zou et al, 2021). In addition, a higher risk of venous thromboembolism has been reported in patients with c-reactive protein flares early after ICI administration (Moik et al, 2022), and increased secretion of various cytokines associated with inflammatory responses may contribute to coagulation abnormalities.…”

Section: Figurementioning

confidence: 99%

Evaluation of cardiovascular toxicity of the atezolizumab and bevacizumab combination

Niimura

Goda

Miyata

et al. 2023

Front. Drug Saf. Regul.

View full text Add to dashboard Cite

Introduction: The combination of atezolizumab, an immune checkpoint inhibitor (ICI), and bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, is the first choice for systemic therapy in hepatocellular carcinoma. Immune-related cardiovascular toxicity—myocarditis and pericarditis—are known to occur during ICI treatment. By contrast, VEGF inhibitors (VEGFIs) cause cardiovascular complications such as hypertension and heart failure. Thus, different cardiovascular toxicities have been recognized for ICIs and VEGFIs, but the impact of their combination remains unclear. Here, we aimed to investigate the cardiovascular toxicity profile of atezolizumab in combination with bevacizumab using the World Health Organization adverse event reporting database—VigiBase.Methods: We analyzed data included in VigiBase till December 2022. To evaluate the frequency of reports related to atezolizumab, bevacizumab, and their combinations for 21 adverse events, we calculated the reporting odds ratio and information component. Analyses of the fatality of various cardiovascular toxicities associated with the use of each drug were performed.Results: The database included 84,951, 10,595, and 2,092 reports of treatment with bevacizumab, atezolizumab, and their combination, respectively. The disproportionality signal of hypertension, arterial embolism and thrombosis, supraventricular tachyarrhythmias, heart failure, myocarditis, hemorrhage-related clinical events, venous embolism and thrombosis, cardiomyopathy, respiratory failure with combination regimen of atezolizumab and bevacizumab was detected. Signals of these adverse events were also detected treatment with either atezolizumab or bevacizumab alone. Venous embolism and thrombosis exhibited the highest fatality rate in the two drug combination (12.82%) relative to those of atezolizumab (6.19%) and bevacizumab (4.54%).Discussion: Cardiovascular toxicity, owing to the combination of atezolizumab and bevacizumab, was similar to that of each single agent, and no new safety concerns were observed. Caution should be exercised when combining the two drugs since the fatality rate of thromboembolism increases with combination treatment.

show abstract

“…Thrombotic complications in cancer patients are common [30,31] and are denominated cancer-associated thrombosis (CAT), but their risk can be influenced by the therapy applied [32][33][34]. Some studies analyzed the relationship between thromboembolic events and ICI treatment in NSCLC patients, showing, for the first time, that the risk of thrombosis is not negligible [33,[35][36][37][38][39]. Further research is needed to discover precise mechanisms underlying the interaction of hemostasis, immunological response and cancer in the context of ICI therapy [29].…”

Section: Introductionmentioning

confidence: 99%

Interaction between NSCLC Cells, CD8+ T-Cells and Immune Checkpoint Inhibitors Potentiates Coagulation and Promotes Metabolic Remodeling—New Cues on CAT-VTE

Freitas-Dias,

Gonçalves,

Martins

et al. 2024

Cells

View full text Add to dashboard Cite

Background: Cancer-associated thrombosis (CAT) and venous thromboembolism (VTE) are frequent cancer-related complications associated with high mortality; thus, this urges the identification of predictive markers. Immune checkpoint inhibitors (ICIs) used in cancer immunotherapy allow T-cell activation against cancer cells. Retrospective studies showed increased VTE following ICI administration in some patients. Non-small cell lung cancer (NSCLC) patients are at high risk of thrombosis and thus, the adoption of immunotherapy, as a first-line treatment, seems to be associated with coagulation-fibrinolysis derangement. Methods: We pharmacologically modulated NSCLC cell lines in co-culture with CD8+ T-cells (TCD8+) and myeloid-derived suppressor cells (MDSCs), isolated from healthy blood donors. The effects of ICIs Nivolumab and Ipilimumab on NSCLC cell death were assessed by annexin V and propidium iodide (PI) flow cytometry analysis. The potential procoagulant properties were analyzed by in vitro clotting assays and enzyme-linked immunosorbent assays (ELISAs). The metabolic remodeling induced by the ICIs was explored by 1H nuclear magnetic resonance (NMR) spectroscopy. Results: Flow cytometry analysis showed that TCD8+ and ICIs increase cell death in H292 and PC-9 cells but not in A549 cells. Conditioned media from NSCLC cells exposed to TCD8+ and ICI induced in vitro platelet aggregation. In A549, Podoplanin (PDPN) levels increased with Nivolumab. In H292, ICIs increased PDPN levels in the absence of TCD8+. In PC-9, Ipilimumab decreased PDPN levels, this effect being rescued by TCD8+. MDSCs did not interfere with the effect of TCD8+ in the production of TF or PDPN in any NSCLC cell lines. The exometabolome showed a metabolic remodeling in NSCLC cells upon exposure to TCD8+ and ICIs. Conclusions: This study provides some insights into the interplay of immune cells, ICIs and cancer cells influencing the coagulation status. ICIs are important promoters of coagulation, benefiting from TCD8+ mediation. The exometabolome analysis highlighted the relevance of acetate, pyruvate, glycine, glutamine, valine, leucine and isoleucine as biomarkers. Further investigation is needed to validate this finding in a cohort of NSCLC patients.

show abstract

Risk Factors, Incidence, and Prognosis of Thromboembolism in Cancer Patients Treated With Immune Checkpoint Inhibitors

Cited by 5 publications

References 64 publications

The Potential Role of Circulating Inflammatory Cells in Predicting the Safety, Efficacy and Immune-related Adverse Events of Immune Check-point Inhibitors: A Narrative Review

The Potential Role of Circulating Inflammatory Cells in Predicting the Safety, Efficacy and Immune-related Adverse Events of Immune Check-point Inhibitors: A Narrative Review

Evaluation of cardiovascular toxicity of the atezolizumab and bevacizumab combination

Interaction between NSCLC Cells, CD8+ T-Cells and Immune Checkpoint Inhibitors Potentiates Coagulation and Promotes Metabolic Remodeling—New Cues on CAT-VTE

Contact Info

Product

Resources

About