scholarly journals Anticoagulation therapy promotes the tumor immune-microenvironment and potentiates the efficacy of immunotherapy by alleviating hypoxia

2021 ◽  
Vol 9 (8) ◽  
pp. e002332
Author(s):  
Jeong Uk Choi ◽  
Na Kyeong Lee ◽  
Hyungseok Seo ◽  
Seung Woo Chung ◽  
Taslim A Al-Hilal ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Oral Anticoagulation ◽  
Oral Anticoagulant ◽  
Tumor Hypoxia ◽  
Anticoagulation Therapy ◽  
Tumor Perfusion ◽  
Immune Microenvironment ◽  
Oral Anticoagulation Therapy ◽  
Tumor Immune Microenvironment ◽  
Immunosuppressive Cytokines

PurposeHere, this study verifies that cancer-associated thrombosis (CAT) accelerates hypoxia, which is detrimental to the tumor immune microenvironment by limiting tumor perfusion. Therefore, we designed an oral anticoagulant therapy to improve the immunosuppressive tumor microenvironment and potentiate the efficacy of immunotherapy by alleviating tumor hypoxia.Experimental designA novel oral anticoagulant (STP3725) was developed to consistently prevent CAT formation. Tumor perfusion and hypoxia were analyzed with or without treating STP3725 in wild-type and P selectin knockout mice. Immunosuppressive cytokines and cells were analyzed to evaluate the alteration of the tumor microenvironment. Effector lymphocyte infiltration in tumor tissue was assessed by congenic CD45.1 mouse lymphocyte transfer model with or without anticoagulant therapy. Finally, various tumor models including K-Ras mutant spontaneous cancer model were employed to validate the role of the anticoagulation therapy in enhancing the efficacy of immunotherapy.ResultsCAT was demonstrated to be one of the perfusion barriers, which fosters immunosuppressive microenvironment by accelerating tumor hypoxia. Consistent treatment of oral anticoagulation therapy was proved to promote tumor immunity by alleviating hypoxia. Furthermore, this resulted in decrease of both hypoxia-related immunosuppressive cytokines and myeloid-derived suppressor cells while improving the spatial distribution of effector lymphocytes and their activity. The anticancer efficacy of αPD-1 antibody was potentiated by co-treatment with STP3725, also confirmed in various tumor models including the K-Ras mutant mouse model, which is highly thrombotic.ConclusionsCollectively, these findings establish a rationale for a new and translational combination strategy of oral anticoagulation therapy with immunotherapy, especially for treating highly thrombotic cancers. The combination therapy of anticoagulants with immunotherapies can lead to substantial improvements of current approaches in the clinic.

scholarly journals The Complication Rates of Oral Anticoagulation Therapy in Deep Venous Thrombosis

2019 ◽  
Vol 65 (3) ◽  
pp. 87-90
Author(s):  
Ionela Silivastru Cozlea ◽  
Arthur-Atilla Keresztesi ◽  
Gabriela Asofie Keresztesi ◽  
Daniel Cozlea ◽  
Daniela Ecaterina Dobru
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Oral Anticoagulation ◽  
Oral Anticoagulant ◽  
Anticoagulation Therapy ◽  
Vitamin K Antagonist ◽  
Complication Rates ◽  
Direct Oral Anticoagulant ◽  
Oral Anticoagulation Therapy ◽  
Hemorrhagic Events

AbstractThe objective of the current study is to evaluate the complication rates (embolic and hemorrhagic events) in deep venous thrombosis (DVT) patients on different types of oral anticoagulation therapy (OAC): direct oral anticoagulant therapy and vitamin K antagonist therapy.Methods: A number of 62 DVT patients were included and divided in two groups, depending on the type of oral anticoagulation therapy administered. The first group was composed of patients treated with direct oral anticoagulant treatment (Dabigatran, Rivaroxaban) and the second group was composed of patients treated with vitamin K antagonist (Acenocumarol). General data, including BMI and comorbidities were noted. Embolic and hemorrhagic events were noticed.Results: in the first group of patients (DOAC therapy), a number of 34 patients were included (14 of them with BMI higher than 25 kg/m2 and 14 with concomitant atrial fibrillation), while the second group comprised of 28 patients treated with VKA (21 of them with a high BMI and only 3 of them with atrial fibrillation). After a mean period of 36 months of anticoagulant therapy, complications were present in 17 patients, hematuria (8 episodes) and pulmonary embolism (4 cases) were the most frequent, with no difference regarding the treatment applied.Conclusion: No statistically significant difference was encountered regarding embolic and hemorrhagic event rates in our deep vein thrombosis patients.

Ervaringen tijdens de "Belgian Improvement Study on Oral Anticoagulation Therapy" (BISOAT)

2005 ◽  
Vol 61 (11) ◽  
pp. 841-847 ◽  
Author(s):  
CLAES N ◽  
BUNTINX F ◽  
VIJGEN J ◽  
ARNOUT J ◽  
VERMYLEN J ◽  
...  
Keyword(s):  
Oral Anticoagulation ◽  
Anticoagulation Therapy ◽  
Oral Anticoagulation Therapy

Depression and Uptake of Oral Anticoagulation Therapy in Patients With Atrial Fibrillation

Medical Care ◽  
2020 ◽  
Vol 58 (3) ◽  
pp. 216-224 ◽  
Author(s):  
Morten Fenger-Grøn ◽  
Claus H. Vestergaard ◽  
Lars Frost ◽  
Dimitry S. Davydow ◽  
Erik T. Parner ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulation ◽  
Anticoagulation Therapy ◽  
Oral Anticoagulation Therapy

scholarly journals Characterizing the Tumor Immune Microenvironment with Tyramide-Based Multiplex Immunofluorescence

2020 ◽  
Vol 25 (4) ◽  
pp. 417-432
Author(s):  
Hidetoshi Mori ◽  
Jennifer Bolen ◽  
Louis Schuetter ◽  
Pierre Massion ◽  
Clifford C. Hoyt ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Multispectral Imaging ◽  
Imaging System ◽  
Predictive Biomarkers ◽  
Cell Types ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Manual Processing ◽  
Cell Densities ◽  
Immune Profiling

AbstractMultiplex immunofluorescence (mIF) allows simultaneous antibody-based detection of multiple markers with a nuclear counterstain on a single tissue section. Recent studies have demonstrated that mIF is becoming an important tool for immune profiling the tumor microenvironment, further advancing our understanding of the interplay between cancer and the immune system, and identifying predictive biomarkers of response to immunotherapy. Expediting mIF discoveries is leading to improved diagnostic panels, whereas it is important that mIF protocols be standardized to facilitate their transition into clinical use. Manual processing of sections for mIF is time consuming and a potential source of variability across numerous samples. To increase reproducibility and throughput we demonstrate the use of an automated slide stainer for mIF incorporating tyramide signal amplification (TSA). We describe two panels aimed at characterizing the tumor immune microenvironment. Panel 1 included CD3, CD20, CD117, FOXP3, Ki67, pancytokeratins (CK), and DAPI, and Panel 2 included CD3, CD8, CD68, PD-1, PD-L1, CK, and DAPI. Primary antibodies were first tested by standard immunohistochemistry and single-plex IF, then multiplex panels were developed and images were obtained using a Vectra 3.0 multispectral imaging system. Various methods for image analysis (identifying cell types, determining cell densities, characterizing cell-cell associations) are outlined. These mIF protocols will be invaluable tools for immune profiling the tumor microenvironment.

Consideration of non-valvular atrial fibrillation with left atrial appendage thrombus formation despite under appropriate oral anticoagulation therapy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Shiraki ◽  
H Tanaka ◽  
K Yamashita ◽  
Y Tanaka ◽  
K Sumimoto ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Oral Anticoagulation ◽  
Left Atrial ◽  
Thrombus Formation ◽  
Anticoagulation Therapy ◽  
Left Ventricular ◽  
Volume Index ◽  
Oral Anticoagulation Therapy

Abstract Background Atrial fibrillation (AF) is the most frequently sustained cardiac arrhythmia, with a prevalence of about 2–3% in the general population. In accordance with CHADS2 or CHA2DS2-VASc score, appropriate oral anticoagulation therapy such as warfarin or direct oral anticoagulants (DOAC) significantly reduced the risk of thromboembolic events. However, left atrial (LA) thrombus can be detected in the LA appendage (LAA) in AF patients despite appropriate oral anticoagulation therapy. Purpose Our purpose was to investigate the associated factors of LAA thrombus formation in non-valvular atrial fibrillation (NVAF) patients despite under appropriate oral anticoagulation therapy. Methods We retrospectively studied consecutive 286 NVAF patients for scheduled catheter ablation or electrical cardioversion for AF in our institution between February 2017 and September 2019. Mean age was 67.1±9.4 years, 79 patients (29.5%) were female, and 140 (52.2%) were paroxysmal AF. All patients underwent transthoracic and transesophageal echocardiography before catheter ablation or electrical cardioversion. All patients received appropriate oral anticoagulation therapy including warfarin or DOAC for at least 3 weeks prior to transesophageal echocardiography based on the current guidelines. LAA thrombus was defined as an echodense intracavitary mass distinct from the underlying endocardium and not caused by pectinate muscles by at least three senior echocardiologists. Results Of 286 NVAF patients with under appropriate oral anticoagulation therapy, LAA thrombus was observed in 9 patients (3.3%). Univariate logistic regression analysis showed that age, paroxysmal AF, CHADS2 score ≥3, left ventricular end-diastolic volume index (LVEDVI), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), LA volume index (LAVI), mitral inflow E and mitral e' annular velocities ratio (E/e'), and LAA flow were associated with LAA thrombus formation. It was noteworthy that multivariate logistic regression analysis showed that LAA flow was independent predictor of LAA thrombus (OR: 0.72, 95% CI: 0.59–0.89, p<0.005) as well as LVEF. Furthermore, receiver operating characteristic (ROC) curve analysis identified the optimal cutoff value of LAA flow for predicting LAA thrombus as ≤15cm/s, with a sensitivity of 88%, specificity of 93%, and area under the curve (AUC) of 0.95. Conclusions LAA flow was strongly associated with LAA thrombus formation even in NVAF patients with appropriate oral anticoagulation therapy. According to our findings, further strengthen of oral anticoagulation therapy or percutaneous transcatheter closure of the LAA may be considered in NVAF patients with appropriate oral anticoagulation therapy but low LAA flow, especially <15cm/s. Funding Acknowledgement Type of funding source: None

scholarly journals The effect of PEGylation on the efficacy and uptake of an immunostimulatory nanoparticle in the tumor immune microenvironment

2021 ◽  
Author(s):  
Wyatt M. Becicka ◽  
Peter Bielecki ◽  
Morgan Lorkowski ◽  
Taylor J. Moon ◽  
Yahan Zhang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Immunosuppressive Tumor Microenvironment

The efficacy of immunotherapies is often limited by the immunosuppressive tumor microenvironment, which is populated with dysfunctional innate immune cells. To reprogram the tumor-resident innate immune cells, we developed an...

Management of Oral Anticoagulation Therapy After Gastrointestinal Bleeding: Whether to, When to, and How to Restart an Anticoagulation Therapy

2017 ◽  
Vol 51 (11) ◽  
pp. 1000-1007 ◽  
Author(s):  
Kazuhiko Kido ◽  
Michael J. Scalese
Keyword(s):  
Gastrointestinal Bleeding ◽  
Cohort Studies ◽  
Oral Anticoagulation ◽  
Retrospective Cohort ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Cochrane Library ◽  
Oral Anticoagulation Therapy ◽  
Retrospective Cohort Studies

Objective: To evaluate current clinical evidence for management of oral anticoagulation therapy after gastrointestinal bleeding (GIB) with an emphasis on whether to, when to, and how to resume an anticoagulation therapy. Data Sources: Relevant articles from MEDLINE, Cochrane Library, and EMBASE databases were identified from 1946 through May 20, 2017, using the keywords: gastrointestinal hemorrhage or gastrointestinal bleeding and antithrombotic therapy or anticoagulation therapy or warfarin or dabigatran or rivaroxaban or apixaban or edoxaban.Study Selection and Data Extraction: All English-language studies assessing management of oral anticoagulation therapy after GIB were evaluated. Data Synthesis: A total of 9 studies were identified. Four retrospective cohort studies showed that resuming anticoagulation therapy was associated with significantly lower rate of thromboembolism (TE) in the general population. Meta-analyses and prospective cohort studies also supported this finding. Two retrospective cohort studies indicated an increase in GIB when anticoagulation reinitiation occurred in less than 7 days without a decrease in TE. Resuming therapy between 7 and 15 days did not demonstrate a significant increase in GIB or TE. A large retrospective study showed that apixaban was associated with the significantly lowest risk of GIB compared with both rivaroxaban and dabigatran. Conclusion: Anticoagulation therapy resumption is recommended, with resumption being considered between 7 and 14 days following GIB regardless of the therapy chosen. Data for warfarin management after GIB should be applied with caution to direct oral anticoagulants (DOACs) because of the quicker onset and experimental nature of reversal agents. Apixaban may be a preferred option when restarting a DOAC therapy.

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