Tumour and microparticle tissue factor expression and cancer thrombosis

Date, Kathryn; Hall, Joseph J.; Greenman, John; Maraveyas, Anthony; Madden, Leigh A.

doi:10.1016/j.thromres.2012.11.013

Cited by 45 publications

(53 citation statements)

References 116 publications

(136 reference statements)

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“…Recent studies have highlighted that after treatment with chemotherapeutic drugs, apoptotic tumor cells can release microparticles, which may contain DAMPs that stimulate DCs and can be used to effectively kill tumor cells. 33,34 Therefore, when appropriate antigenic transfer to DCs occurs, the acute release of DAMPs may help to elicit immune responses in cancer-bearing patients. Maturation and activation of DCs is required for DC migration to T-cell regions within the lymph node.…”

Section: Discussionmentioning

confidence: 99%

TLR4 is essential for dendritic cell activation and anti-tumor T-cell response enhancement by DAMPs released from chemically stressed cancer cells

et al. 2013

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The combination of immunotherapy and chemotherapy is regarded as a promising approach for the treatment of certain types of cancer. However, the underlying mechanisms need to be fully investigated to guide the design of more efficient protocols for cancer chemoimmunotherapy. It is well known that danger-associated molecular patterns (DAMPs) can activate immune cells, including dendritic cells (DCs), via Toll-like receptors (TLRs); however, the role of DAMPs released from chemical drug-treated tumor cells in the activation of the immune response needs to be further elucidated. Here, we found that colorectal cancer (CRC) cells treated with oxaliplatin (OXA) and/or 5-fluorouracil (5-Fu) released high levels of high-mobility group box 1 (HMGB1) and heat shock protein 70 (HSP70). After OXA/5-Fu therapy, the sera of CRC patients also exhibited increased levels of HMGB1 and HSP70, both of which are well-known DAMPs. The supernatants of dying CRC cells treated with OXA/5-Fu promoted mouse and human DC maturation, with upregulation of HLA-DR, CD80 and CD86 expression and enhancement of IL-1b, TNF-a, MIP-1a, MIP-1b, RANTES and IP-10 production. Vaccines composed of DCs pulsed with the supernatants of chemically stressed CRC cells induced a more significant IFN-c-producing Th1 response both in vitro and in vivo. However, the supernatants of chemically stressed CRC cells failed to induce phenotypic maturation and cytokine production in TLR4-deficient DCs, indicating an essential role of TLR4 in DAMP-induced DC maturation and activation. Furthermore, pulsing with the supernatants of chemically stressed CRC cells did not efficiently induce an IFN-c-producing Th1 response in TLR4-deficient DCs. Collectively, these results demonstrate that DAMPs released from chemically stressed cancer cells can activate DCs via TLR4 and enhance the induction of an anti-tumor T-cell immune response, delineating a clinically relevant immuno-adjuvant pathway triggered by DAMPs.

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Section: Discussionmentioning

confidence: 99%

TLR4 is essential for dendritic cell activation and anti-tumor T-cell response enhancement by DAMPs released from chemically stressed cancer cells

et al. 2013

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“…Some microparticles contribute to coagulation through various other mechanisms (e.g., tissue factor expression) (69,84,86,(90)(91)(92). Certain microparticles may also act as inhibitors of coagulation, adding complexity to the function microparticles play in regulating coagulation homeostasis (69).…”

Section: Focused Reviewsmentioning

confidence: 99%

Review of the Association between Splenectomy and Chronic Thromboembolic Pulmonary Hypertension

Kimmig

Palevsky

2016

Annals ATS

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Recent evidence suggests that there may be a link between splenectomy and the later development of pulmonary hypertension, in particular World Health Organization group IV pulmonary hypertension (chronic thromboembolic pulmonary hypertension). Epidemiological studies have demonstrated an odds ratio as high as 18 for the development of chronic thromboembolic pulmonary hypertension after splenectomy in comparison with matched control subjects who have not undergone splenectomy. The mechanisms governing the association between removal of the spleen and the subsequent development of chronic thromboembolic pulmonary hypertension remain incompletely understood; however, recent advances in understanding of coagulation homeostasis have shed some light on this association. Splenectomy increases the risk of venous thromboembolic disease, a necessary precursor of chronic thromboembolic pulmonary hypertension, by generating a prothrombotic state. This prothrombotic state likely results from a reduction in the removal of circulating procoagulant factors from the bloodstream after splenectomy. Although much is to be learned, circulating microparticles have emerged as the most likely mediator for the development of thrombosis after splenectomy. Apparently because of a reduction in reticuloendothelial cell clearance, microparticle levels are elevated in patients after splenectomy. Elevated circulating microparticle levels have been linked to thromboembolism and pulmonary hypertension in a dose-dependent fashion. It is important for health care providers to be aware of the link between splenectomy and chronic thromboembolic pulmonary hypertension. We are optimistic that clarification of the exact mechanisms that govern this association will yield clinical guidelines and potential treatments.

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“…Tissue factor is constitutively present on the surface of malignant tumors which activates platelets (Callander et al, 1992; Date et al, 2013), and is shed on tumor microvesicles (Yu and Rak, 2004). Tissue factor generates thrombin, which has been shown to induce platelet-tumor cell interactions in vitro , and administration of thrombin increases pulmonary metastases in murine models of colon cancer (summarized in Gay and Felding-Habermann, 2011).…”

Section: Platelets and Cancer Progressionmentioning

confidence: 99%

Cancer and Thrombosis: The Platelet Perspective

Meikle

Kelly

Garg

et al. 2017

Front. Cell Dev. Biol.

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Platelets are critical to hemostatic and immunological function, and are key players in cancer progression, metastasis, and cancer-related thrombosis. Platelets interact with immune cells to stimulate anti-tumor responses and can be activated by immune cells and tumor cells. Platelet activation can lead to complex interactions between platelets and tumor cells. Platelets facilitate cancer progression and metastasis by: (1) forming aggregates with tumor cells; (2) inducing tumor growth, epithelial-mesenchymal transition, and invasion; (3) shielding circulating tumor cells from immune surveillance and killing; (4) facilitating tethering and arrest of circulating tumor cells; and (5) promoting angiogenesis and tumor cell establishment at distant sites. Tumor cell-activated platelets also predispose cancer patients to thrombotic events. Tumor cells and tumor-derived microparticles lead to thrombosis by secreting procoagulant factors, resulting in platelet activation and clotting. Platelets play a critical role in cancer progression and thrombosis, and markers of platelet-tumor cell interaction are candidates as biomarkers for cancer progression and thrombosis risk.

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Tumour and microparticle tissue factor expression and cancer thrombosis

Cited by 45 publications

References 116 publications

TLR4 is essential for dendritic cell activation and anti-tumor T-cell response enhancement by DAMPs released from chemically stressed cancer cells

TLR4 is essential for dendritic cell activation and anti-tumor T-cell response enhancement by DAMPs released from chemically stressed cancer cells

Review of the Association between Splenectomy and Chronic Thromboembolic Pulmonary Hypertension

Cancer and Thrombosis: The Platelet Perspective

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