The pro-inflammatory role of platelets in cancer

Olsson, Anna‐Karin; Cedervall, Jessica

doi:10.1080/09537104.2018.1453059

Cited by 98 publications

(97 citation statements)

References 73 publications

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“…The literature also supports the association of elevated platelet counts with lung cancer risk 59 . Still it is plausible that thrombocytes could contribute to tumor progression by stimulating angiogenesis 67 and activating thrombosis-related inflammation 68 . In addition, observational studies have found that the composition of blood cells including neutrophil-lymphocyte ratio and thrombocyte-lymphocyte ratio are associated with overall and disease-free survival in multiple cancers 69 .…”

Section: Discussionmentioning

confidence: 99%

Mosaic chromosome Y loss is associated with alterations in blood cell counts in UK Biobank men

Lin

Loftfield

Sampson

et al. 2020

Sci Rep

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Mosaic loss of Y chromosome (mLoY) is the most frequently detected somatic copy number alteration in leukocytes of men. in this study, we investigate blood cell counts as a potential mechanism linking mLOY to disease risk in 206,353 UK males. Associations between mLOY, detected by genotyping arrays, and blood cell counts were assessed by multivariable linear models adjusted for relevant risk factors. Among the participants, mLOY was detected in 39,809 men. We observed associations between mLoY and reduced erythrocyte count (−0.009 [−0.014, −0.005] × 10 12 cells/L, p = 2.75 × 10 −5) and elevated thrombocyte count (5.523 [4.862, 6.183] × 10 9 cells/L, p = 2.32 × 10 −60) and leukocyte count (0.218 [0.198, 0.239] × 10 9 cells/L, p = 9.22 × 10 −95), particularly for neutrophil count (0.174 × [0.158, 0.190]10 9 cells/L, p = 1.24 × 10 −99) and monocyte count (0.021 [0.018 to 0.024] × 10 9 cells/L, p = 6.93 × 10 −57), but lymphocyte count was less consistent (0.016 [0.007, 0.025] × 10 9 cells/L, p = 8.52 × 10 −4). Stratified analyses indicate these associations are independent of the effects of aging and smoking. Our findings provide population-based evidence for associations between mLOY and blood cell counts that should stimulate investigation of the underlying biological mechanisms linking mLoY to cancer and chronic disease risk. Recently, large molecular epidemiology studies have shown that hematopoietic cells can undergo postzygotic mutations resulting in somatic copy number alterations, which can give rise to daughter cells with the same genomic aberration. Clonal expansion of cells bearing a somatic mutation results in clonal mosaicism 1. Clonal mosaicism can be driven by somatic mutations affecting genes frequently mutated in myelodysplastic disease (referred to as clonal hematopoiesis of indeterminate potential (CHIP)) 2 or be the result of acquired copy number aberrations. The most frequently detected somatic copy number alteration in circulating leukocytes is mosaic loss of the Y chromosome (mLOY) in males 3-5. The prevalence of mLOY is age-related, increasing substantially after age 50 in men. Likewise, CHIP is common in the elderly, with recent evidence suggesting CHIP and mLOY may co-occur 6. Exposure to cigarette smoking 4,7 has also been well established as a risk factor for mLOY and recently, early evidence suggests that air pollution could also be associated with mLOY 8. Epidemiologic studies have uncovered potential associations between mLOY and increased risk of cancer 3-5 , neurodegenerative diseases 9 , and cardiovascular diseases 10,11. Similarly, CHIP has been associated with select cancers and cardiovascular disease 2. Although common germline variants near important cell-cycle regulation and cancer susceptibility genes have been identified through genome-wide association studies of mLOY 4,12 , the underlying biologic mechanisms linking mLOY to chronic disease risk are likely complex. We investigated possible associations between mLOY and clinical measures, here the composition of the classical h...

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Section: Discussionmentioning

confidence: 99%

Mosaic chromosome Y loss is associated with alterations in blood cell counts in UK Biobank men

Lin

Loftfield

Sampson

et al. 2020

Sci Rep

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“…ANC, as a measure of systemic inflammatory response to malignancy, is linked to immunosuppression in certain tumors . Furthermore, platelets can be stimulated by systemic inflammation through several pro‐inflammatory factors, such as IL‐1, IL‐3, and IL‐6, and platelet aggregation and degranulation leads to the release of platelet‐derived proangiogenic mediators, which have been suggested to promote tumor growth .…”

Section: Discussionmentioning

confidence: 99%

Complete Blood Count Score Model Integrating Reduced Lymphocyte-Monocyte Ratio, Elevated Neutrophil-Lymphocyte Ratio, and Elevated Platelet-Lymphocyte Ratio Predicts Inferior Clinical Outcomes in Adult T-Lymphoblastic Lymphoma

Feng

et al. 2019

The Oncologist

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Background T‐lymphoblastic lymphoma (T‐LBL) is a highly aggressive neoplasm of lymphoblasts of T‐cell origin. Although promising improvements have been recently achieved, one third of patients experience relapse or refractory T‐LBL. Therefore, optimal strategies for identifying high‐risk patients are urgently needed. Materials and Methods In the present study, 75 newly diagnosed adult patients (aged ≥15 years) with T‐LBL were identified and the predictive value of complete blood count (CBC) abnormalities, including lymphocyte‐monocyte ratio (LMR), neutrophil‐lymphocyte ratio (NLR), and platelet‐lymphocyte ratio (PLR) on clinical outcomes, was analyzed. Results Using the receiver operating characteristic curve to determine the best cutoff values based on survival, it was found that patients with T‐LBL with LMR ≤2.8, NLR ≥3.3, and PLR ≥200 had both inferior progression‐free survival (PFS) and inferior overall survival (OS), in which the differences were much more remarkable in the international prognostic index score 0–2 subgroup. In the multivariable analysis, NLR ≥3.3 together with age >40 years and central nervous system (CNS) involvement were identified to be independently associated with shortened PFS, whereas PLR ≥200 and CNS involvement were identified to be independent risk factors for OS. LMR, NLR, and PLR were integrated to generate a “CBC score” model, which well separated adult patients with T‐LBL into three risk groups, and the 3‐year OS was 84%, 53%, and 30% for low‐, intermediate‐, and high‐risk patients, respectively. Conclusion Overall, a “CBC score” model was initially promoted for stratification in adult patients with T‐LBL using simple, widely available, and easy to interpret parameters in the largest adult T‐LBL cohort to date. Implications for Practice Optimal strategies for identifying high‐risk patients with T‐lymphoblastic lymphoma (T‐LBL) are urgently needed. In the largest adult T‐LBL cohort to date, simple, inexpensive, widely available parameters were applied and revealed that patients with lymphocyte‐monocyte ratio (LMR) ≤2.8, neutrophil‐lymphocyte ratio (NLR) ≥3.3, and platelet‐lymphocyte ratio (PLR) ≥200 had both inferior progression‐free survival and inferior overall survival (OS), in which the differences were much more remarkable in the international prognostic index score 0–2 subgroup. LMR, NLR, and PLR were integrated to generate a “complete blood count score” model, in which the 3‐year OS was 84%, 53%, and 30% for low‐, intermediate‐, and high‐risk patients, respectively.

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“…Various types of tumor cells and tumor-derived ECs can activate platelets by different mechanisms. There is plenty of evidence that activated platelets exert their pleiotropic effects on many biological processes central to angiogenesis, progression, inflammation and metastasis in various tumor types [57,60,61]. Improving our understanding of such platelet involvement in neovascularization may potentially help in the development of alternative treatment strategies for patients with KHE.…”

Section: Platelet Aggregation: a Key Trigger Of Kmp?mentioning

confidence: 99%

Kaposiform hemangioendothelioma: current knowledge and future perspectives

Chen

Yang

et al. 2020

Orphanet J Rare Dis

120

180

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Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm with high morbidity and mortality. The initiating mechanism during the pathogenesis of KHE has yet to be discovered. The main pathological features of KHE are abnormal angiogenesis and lymphangiogenesis. KHEs are clinically heterogeneous and may develop into a lifethreatening thrombocytopenia and consumptive coagulopathy, known as the Kasabach-Merritt phenomenon (KMP). The heterogeneity and the highly frequent occurrence of disease-related comorbidities make the management of KHE challenging. Currently, there are no medications approved by the FDA for the treatment of KHE. Multiple treatment regimens have been used with varying success, and new clinical trials are in progress. In severe patients, multiple agents with variable adjuvant therapies are given in sequence or in combination. Recent studies have demonstrated a satisfactory efficacy of sirolimus, an inhibitor of mammalian target of rapamycin, in the treatment of KHE. Novel targeted treatments based on a better understanding of the pathogenesis of KHE are needed to maximize patient outcomes and quality of life. This review summarizes the epidemiology, etiology, pathophysiology, clinical features, diagnosis and treatments of KHE. Recent new concepts and future perspectives for KHE will also be discussed.

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The pro-inflammatory role of platelets in cancer

Cited by 98 publications

References 73 publications

Mosaic chromosome Y loss is associated with alterations in blood cell counts in UK Biobank men

Mosaic chromosome Y loss is associated with alterations in blood cell counts in UK Biobank men

Complete Blood Count Score Model Integrating Reduced Lymphocyte-Monocyte Ratio, Elevated Neutrophil-Lymphocyte Ratio, and Elevated Platelet-Lymphocyte Ratio Predicts Inferior Clinical Outcomes in Adult T-Lymphoblastic Lymphoma

Kaposiform hemangioendothelioma: current knowledge and future perspectives

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