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Research progress on exosomes derived from mesenchymal stem cells in hematological malignancies.

Mesenchymal stem cells (MSCs) are a subset of multifunctional stem cells with self-renewal and multidirectional differentiation properties that play a pivotal role in tumor progression. MSCs are reported to exert biological functions by secreting specialized vesicles, known as exosomes, with tumor cells. Exosomes participate in material and information exchange between cells and are crucial in multiple physiological and pathological processes. This study provides a comprehensive overview of the roles, mechanisms of action and sources of MSC exosomes in hematological malignancies, and different

Understanding the Progression of Bone Metastases to Identify Novel Therapeutic Targets.

Bone is one of the most preferential target site for cancer metastases, particularly for prostate, breast, kidney, lung and thyroid primary tumours. Indeed, numerous chemical signals and growth factors produced by the bone microenvironment constitute factors promoting cancer cell invasion and aggression. After reviewing the different theories proposed to provide mechanism for metastatic progression, we report on the gene expression profile of bone-seeking cancer cells. We also discuss the cross-talk between the bone microenvironment and invading cells, which impacts on the tumour actions on su

Proteolytic chemokine cleavage as a regulator of lymphocytic infiltration in solid tumors.

In the past decade, immune-based therapies such as monoclonal antibodies against tumor epitopes or immune checkpoint inhibitors have become an integral part of contemporary cancer treatment in many entities. However, a fundamental prerequisite for the success of such therapies is a sufficient trafficking of tumor-infiltrating lymphocytes into the tumor microenvironment. This infiltration is facilitated by chemokines, a group of about 50 small proteins capable of chemotactically guiding leukocytes. Proteolytic inactivation of chemokines leading to an impaired infiltration of immune effector cel

Megakaryocyte Contribution to Bone Marrow Fibrosis: many Arrows in the Quiver.

In Primary Myelofibrosis (PMF), megakaryocyte dysplasia/hyperplasia determines the release of inflammatory cytokines that, in turn, stimulate stromal cells and induce bone marrow fibrosis. The pathogenic mechanism and the cells responsible for progression to bone marrow fibrosis in PMF are not completely understood. This review article aims to provide an overview of the crucial role of megakaryocytes in myelofibrosis by discussing the role and the altered secretion of megakaryocyte-derived soluble factors, enzymes and extracellular matrices that are known to induce bone marrow fibrosis.

Pathophysiological Roles of the CX3CL1-CX3CR1 Axis in Renal Disease, Cardiovascular Disease, and Cancer.

CX3CL1 and its unique receptor, CX3CR1, are leukocyte migration factors and are involved in the pathogenesis and progression of many inflammatory diseases and malignancies. The CX3CL1-CX3CR1 axis induces a variety of responses, including cell proliferation, migration, invasion, and apoptosis resistance. CX3CL1 is a transmembrane protein, and proteolysis generates a soluble form. The membrane and soluble forms of CX3CL1 exhibit different functions, but both bind to the chemokine receptor CX3CR1. The CX3CL1-CX3CR1 axis is a chemokine system that has attracted attention not only as a therapeutic

How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.

Cancer remains the leading cause of mortality worldwide. Radiotherapy (RT), a cornerstone of oncological treatment for over a century, has achieved great success in various cancers. However, radioresistance remains the primary factor leading to the failure of radiotherapy. Histone modifications in cancer cells are known to play a pivotal role in regulating radiosensitivity by modulating chromatin structure, either by loosening or tightening it. Here, we provide a comprehensive summary of the link between aberrant histone modifications and radiation resistance across various cancer and normal t

Current Status of 68Ga-Pentixafor in Solid Tumours.

Chemokine receptor CXCR4 is overexpressed in neoplasms and its expression is related to tumour invasion, metastasis and aggressiveness. 68Ga-Pentixafor is used to non-invasively image the expression of CXCR4 in tumours and has been widely used in haematological malignancies. Recent evidence shows that therapies targeting CXCR4 can increase the chemosensitivity of the tumour as well as inhibit tumour metastasis and aggressiveness. 68Ga-Pentixafor has shown promise as an elegant radiotracer to aid in the selection of patients whose tumours demonstrate CXCR4 overexpression and who therefore may b

Communication in the Cancer Microenvironment as a Target for Therapeutic Interventions.

The tumor microenvironment (TME) is a complex system composed of multiple cells, such as non-cancerous fibroblasts, adipocytes, immune and vascular cells, as well as signal molecules and mediators. Tumor cells recruit and reprogram other cells to produce factors that maintain tumor growth. Communication between cancerous and surrounding cells is a two-way process and engages a diverse range of mechanisms that, in consequence, can lead to rapid proliferation, metastasis, and drug resistance, or can serve as a tumors-suppressor, e.g., through tumor-immune cell interaction. Cross-talk within the

Targeting NETosis: nature's alarm system in cancer progression.

Neutrophils are recognized active participants in inflammatory responses and are intricately linked to cancer progression. In response to inflammatory stimuli, neutrophils become activated, releasing neutrophils extracellular traps (NETs) for the capture and eradication of pathogens, a phenomenon termed NETosis. With a deeper understanding of NETs, there is growing evidence supporting their role in cancer progression and their involvement in conferring resistance to various cancer therapies, especially concerning tumor reactions to chemotherapy, radiation therapy (RT), and immunotherapy. This

The role of exosomes in lung cancer metastasis and clinical applications: an updated review.

Lung cancer is the leading cause of cancer-associated deaths accounting for 24% of all cancer deaths. As a crucial phase of tumor progression, lung cancer metastasis is linked to over 70% of these mortalities. In recent years, exosomes have received increasing research attention in their role in the induction of carcinogenesis and metastasis in the lung. In this review, recent studies on the contribution of exosomes to lung cancer metastasis are discussed, particularly highlighting the role of lung tumor-derived exosomes in immune system evasion, epithelial-mesenchymal transition, and angiogen

Contribution of Macrophages and T Cells in Skeletal Metastasis.

Bone is a common site for metastases with a local microenvironment that is highly conducive for tumor establishment and growth. The bone marrow is replete with myeloid and lymphoid linage cells that provide a fertile niche for metastatic cancer cells promoting their survival and growth. Here, we discuss the role of macrophages and T cells in pro- and anti-tumoral mechanisms, their interaction to support cancer cell growth, and their contribution to the development of skeletal metastases. Importantly, immunotherapeutic strategies targeting macrophages and T cells in cancer are also discussed in

Osteoimmuno-Oncology: Therapeutic Opportunities for Targeting Immune Cells in Bone Metastasis.

Immunotherapies provide a potential treatment option for currently incurable bone metastases. Bone marrow is an important secondary lymphoid organ with a unique immune contexture. Even at non-disease state immune cells and bone cells interact with each other, bone cells supporting the development of immune cells and immune cells regulating bone turnover. In cancer, tumor cells interfere with this homeostatic process starting from formation of pre-metastatic niche and later supporting growth of bone metastases. In this review, we introduce a novel concept osteoimmuno-oncology (OIO), which refer

Cancer Resistance to Immunotherapy: Comprehensive Insights with Future Perspectives.

Cancer immunotherapy is a type of treatment that harnesses the power of the immune systems of patients to target cancer cells with better precision compared to traditional chemotherapy. Several lines of treatment have been approved by the US Food and Drug Administration (FDA) and have led to remarkable success in the treatment of solid tumors, such as melanoma and small-cell lung cancer. These immunotherapies include checkpoint inhibitors, cytokines, and vaccines, while the chimeric antigen receptor (CAR) T-cell treatment has shown better responses in hematological malignancies. Despite these

Exploring the applicability, combined strategies, and challenges of ablation in hematology based on its characteristics and immunomodulatory mechanisms.

Malignant hematological diseases, such as lymphoma, leukemia, and multiple myeloma, are frequently accompanied by clinical challenges including local progressive lesions, relapsed/refractory conditions, and poor tolerance to standard treatments in special populations. Systemic therapies represented by chemotherapy and targeted therapy have inherent limitations in addressing local tumor burden, relieving organ compression, and being suitable for frail patients. As a minimally invasive local treatment technology, ablation has been widely used in solid tumor therapy due to its advantages of preci

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… It should be noted that incomplete microwave ablation (iMWA) may induce an inhibitory tumor microenvironment (TME). iMWA can promote the chemokine CXCL5, leading to a decrease in CD4 + T cells, CD8 + T cells, natural killer (NK) cells, and macrophages (including M1 and M2 types), but an increase in monocytes …

Balancing the Scales: The Dual Role of Interleukins in Bone Metastatic Microenvironments.

Bone metastases, a common and debilitating consequence of advanced cancers, involve a complex interplay between malignant cells and the bone microenvironment. Central to this interaction are interleukins (ILs), a group of cytokines with critical roles in immune modulation and inflammation. This review explores the dualistic nature of pro-inflammatory and anti-inflammatory interleukins in bone metastases, emphasizing their molecular mechanisms, pathological impacts, and therapeutic potential. Pro-inflammatory interleukins, such as IL-1, IL-6, and IL-8, have been identified as key drivers in pro

Chemokines and their receptors in oral squamous cell carcinoma: mechanisms, clinical significance, and therapeutic implications.

Chemokines, a category of cytokines exhibiting chemotactic properties, have been thoroughly investigated as targets in cancer treatment in recent decades. In oral squamous cell carcinoma (OSCC), a prevalent and high-risk malignancy of the head and neck, chemokines interact with their specific receptors to initiate downstream signaling pathways. This signaling influences not only tumor cell proliferation, migration, invasion, and metastasis of oral cancer cells but also angiogenesis and vascular maturation. Furthermore, they modulate the tumor microenvironment (TME), which consists of diverse c

COVID-19 signalome: Pathways for SARS-CoV-2 infection and impact on COVID-19 associated comorbidity.

The COVID-19 pandemic has been the focus of research the past two years. The major breakthrough was made by discovering pathways related to SARS-CoV-2 infection through cellular interaction by angiotensin-converting enzyme (ACE2) and cytokine storm. The presence of ACE2 in lungs, intestines, cardiovascular tissues, brain, kidneys, liver, and eyes shows that SARS-CoV-2 may have targeted these organs to further activate intracellular signalling pathways that lead to cytokine release syndrome. It has also been reported that SARS-CoV-2 can hijack coatomer protein-I (COPI) for S protein retrograde

Cancer Immunotherapy with Immune Checkpoint Inhibitors-Biomarkers of Response and Toxicity; Current Limitations and Future Promise.

Immune checkpoint inhibitors are monoclonal antibodies that are used to treat over one in three cancer patients. While they have changed the natural history of disease, prolonging life and preserving quality of life, they are highly active in less than 40% of patients, even in the most responsive malignancies such as melanoma, and cause significant autoimmune side effects. Licenced biomarkers include tumour Programmed Death Ligand 1 expression by immunohistochemistry, microsatellite instability, and tumour mutational burden, none of which are particularly sensitive or specific. Emerging tumour

Bone Marrow Mesenchymal Stromal Cells in Multiple Myeloma: Their Role as Active Contributors to Myeloma Progression.

Multiple myeloma (MM) is a hematological malignancy of plasma cells that proliferate and accumulate within the bone marrow (BM). Work from many groups has made evident that the complex microenvironment of the BM plays a crucial role in myeloma progression and response to therapeutic agents. Within the cellular components of the BM, we will specifically focus on mesenchymal stromal cells (MSCs), which are known to interact with myeloma cells and the other components of the BM through cell to cell, soluble factors and, as more recently evidenced, through extracellular vesicles. Multiple structur

Natural Killer Cells in the Malignant Niche of Multiple Myeloma.

Natural killer (NK) cells represent a subset of CD3- CD7+ CD56+/dim lymphocytes with cytotoxic and suppressor activity against virus-infected cells and cancer cells. The overall potential of NK cells has brought them to the spotlight of targeted immunotherapy in solid and hematological malignancies, including multiple myeloma (MM). Nonetheless, NK cells are subjected to a variety of cancer defense mechanisms, leading to impaired maturation, chemotaxis, target recognition, and killing. This review aims to summarize the available and most current knowledge about cancer-related impairment of NK c