The Role of Extracellular Vesicles in the Pathogenesis of Hematological Malignancies: Interaction with Tumor Microenvironment; a Potential Biomarker and Targeted Therapy

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Blood coagulation and cancer are intrinsically connected, hypercoagulation-associated thrombotic complications are commonly observed in certain types of cancer, often leading to decreased survival in cancer patients. Apart from the common role in coagulation, coagulation proteases often trigger intracellular signaling in various cancers via the activation of a G protein-coupled receptor superfamily protease: protease-activated receptors (PARs). Although the role of PARs is well-established in the development and progression of certain types of cancer, their impact on cancer immune response is only just emerging. The present review highlights how coagulation protease-driven PAR signaling plays a key role in modulating innate and adaptive immune responses. This is followed by a detailed discussion on the contribution of coagulation protease-induced signaling in cancer immune evasion, thereby supporting the growth and development of certain tumors. A special section of the review demonstrates the role of coagulation proteases, thrombin, factor VIIa, and factor Xa in cancer immune evasion. Targeting coagulation protease-induced signaling might be a potential therapeutic strategy to boost the immune surveillance mechanism of a host fighting against cancer, thereby augmenting the clinical consequences of targeted immunotherapeutic regimens.

Section: Biomarkers For Thrombosis Associated With Immune Checkpoint ...mentioning

confidence: 99%

Coagulation Protease-Driven Cancer Immune Evasion: Potential Targets for Cancer Immunotherapy

Paul,

Mukherjee,

Das

2024

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“…A growing body of evidence confirms that exosomes, by transporting numerous pro-angiogenic biomolecules like vascular endothelial growth factors (VEGFs), matrix metalloproteinases (MMPs) and microRNAs, may participate in cancer angiogenesis and progression [125]. EVs carry bioactive molecules from the originating cells and interact with immune cells, stromal cells and endothelial cells in the TME [126]. They can be considered as predictive biomarkers, drug carriers and therapeutic targets in hematological malignancies [127][128][129].…”

Section: Extracellular Vesicles (Evs)mentioning

confidence: 99%

Emerging Therapeutic Targets and Drug Resistance Mechanisms in Immunotherapy of Hematological Malignancies

Olejarz,

Basak

2023

CAR-T cell therapy has revolutionized the treatment of hematological malignancies with high remission rates in the case of ALL and NHL. This therapy has some limitations such as long manufacturing periods, persistent restricted cell sources and high costs. Moreover, combination regimens increase the risk of immune-related adverse events, so the identification new therapeutic targets is important to minimize the risk of toxicities and to guide more effective approaches. Cancer cells employ several mechanisms to evade immunosurveillance, which causes resistance to immunotherapy; therefore, a very important therapeutic approach is to focus on the development of rational combinations of targeted therapies with non-overlapping toxicities. Recent progress in the development of new inhibitory clusters of differentiation (CDs), signaling pathway molecules, checkpoint inhibitors, and immunosuppressive cell subsets and factors in the tumor microenvironment (TME) has significantly improved anticancer responses. Novel strategies regarding combination immunotherapies with CAR-T cells are the most promising approach to cure cancer.

“…HL comprise a diverse cell population, including characteristic lymphoid and myeloid lineage cells. These tumor cells can engage with the vascular microenvironment, thereby influencing angiogenesis, immune responses, and inflammation associated with HL [56].…”

Section: Molecular Network In Hlmentioning

confidence: 99%

“…HL is characterized by a disruption in the microenvironment, where Reed-Sternberg cells contribute to the release of cytokines such as IL-13, IL-10, and TGF-β, along with chemokines and growth factors. These elements alter the cellular composition and immune functions [56,64]. Reed-Sternberg cells produce and release chemokines that attract other immune cells to the tumor site, which in turn negatively affects the recognition and attack of tumor cells [52].…”

Section: Molecular Network In Hlmentioning

confidence: 99%

Potential Associations between Vascular Biology and Hodgkin’s Lymphoma: An Overview

Rodrigues,

Miguel,

Abreu

et al. 2023

Hodgkin’s lymphoma (HL) is a lymphatic neoplasm typically found in the cervical lymph nodes. The disease is multifactorial, and in recent years, the relationships between various vascular molecules have been explored in the field of vascular biology. The connection between vascular biology and HL is intricate and the roles of several pathways remain unclear. This review summarizes the cellular and molecular relationships between vascular biology and HL. Proteins associated with various functions in vascular biology, including cytokines (TNF-α, IL-1, IL-13, and IL-21), chemokines (CXCL10, CXCL12, and CCL21), adhesion molecules (ELAM-1/VCAM-1), and growth factors (BDNF/NT-3, platelet-derived growth factor receptor-α), have been linked to tumor activity. Notable tumor activities include the induction of paracrine activation of NF-kB-dependent pathways, upregulation of adhesion molecule regulation, genome amplification, and effective loss of antigen presentation mediated by MHC-II. Preclinical study models, primarily those using cell culture, have been optimized for HL. Animal models, particularly mice, are also used as alternatives to complex biological systems, with studies primarily focusing on the physiopathogenic evaluation of the disease. These biomolecules warrant further study because they may shed light on obscure pathways and serve as targets for prevention and/or treatment interventions.