-
Human Vaccines & Immunotherapeutics Dec 2023For decades, immunotherapies have offered hope for patients with advanced cancer. However, they show distinct benefits and limited clinical effects. Tumor vaccines have... (Review)
Review
For decades, immunotherapies have offered hope for patients with advanced cancer. However, they show distinct benefits and limited clinical effects. Tumor vaccines have the potential to prime tumor-antigen-specific T cells and induce broad subsets of immune responses, ultimately eradicating tumor cells. Here, we classify tumor vaccines by their anti-tumor mechanisms, which include boosting the immune system, overcoming tumor immunosuppression, and modulating tumor angiogenesis. We focus on multidimensional tumor vaccine strategies using combinations of two or three of the above mechanisms, as these are superior to single-dimensional treatments. This review offers a perspective on tumor vaccine strategies and the future role of vaccine therapies in cancer treatment.
Topics: Humans; Cancer Vaccines; Neoplasms; Immunotherapy; Antigens, Neoplasm; T-Lymphocytes
PubMed: 37905395
DOI: 10.1080/21645515.2023.2271334 -
Cells Jul 2023CD93 (also known as complement protein 1 q subcomponent receptor C1qR1 or C1qRp), is a transmembrane glycoprotein encoded by a gene located on 20p11.21 and composed of... (Review)
Review
CD93 (also known as complement protein 1 q subcomponent receptor C1qR1 or C1qRp), is a transmembrane glycoprotein encoded by a gene located on 20p11.21 and composed of 652 amino acids. CD93 can be present in two forms: soluble (sCD93) and membrane-bound (CD93). CD93 is mainly expressed on endothelial cells, where it plays a key role in promoting angiogenesis both in physiology and disease, such as age-related macular degeneration and tumor angiogenesis. In fact, CD93 is highly expressed in tumor-associated vessels and its presence correlates with a poor prognosis, poor immunotherapy response, immune cell infiltration and high tumor, node and metastasis (TNM) stage in many cancer types. CD93 is also expressed in hematopoietic stem cells, cytotrophoblast cells, platelets and many immune cells, i.e., monocytes, neutrophils, B cells and natural killer (NK) cells. Accordingly, CD93 is involved in modulating important inflammatory-associated diseases including systemic sclerosis and neuroinflammation. Finally, CD93 plays a role in cardiovascular disease development and progression. In this article, we reviewed the current literature regarding the role of CD93 in modulating angiogenesis, inflammation and tumor growth in order to understand where this glycoprotein could be a potential therapeutic target and could modify the outcome of the abovementioned pathologies.
Topics: Humans; Endothelial Cells; Inflammation; Monocytes; Neovascularization, Pathologic
PubMed: 37443812
DOI: 10.3390/cells12131778 -
Frontiers in Oncology 2024Angiogenesis is essential for tumour growth and metastasis. Antiangiogenic factor-targeting drugs have been approved as first line agents in a variety of oncology... (Review)
Review
Angiogenesis is essential for tumour growth and metastasis. Antiangiogenic factor-targeting drugs have been approved as first line agents in a variety of oncology treatments. Clinical drugs frequently target the VEGF signalling pathway during sprouting angiogenesis. Accumulating evidence suggests that tumours can evade antiangiogenic therapy through other angiogenesis mechanisms in addition to the vascular sprouting mechanism involving endothelial cells. These mechanisms include (1) sprouting angiogenesis, (2) vasculogenic mimicry, (3) vessel intussusception, (4) vascular co-option, (5) cancer stem cell-derived angiogenesis, and (6) bone marrow-derived angiogenesis. Other non-sprouting angiogenic mechanisms are not entirely dependent on the VEGF signalling pathway. In clinical practice, the conversion of vascular mechanisms is closely related to the enhancement of tumour drug resistance, which often leads to clinical treatment failure. This article summarizes recent studies on six processes of tumour angiogenesis and provides suggestions for developing more effective techniques to improve the efficacy of antiangiogenic treatment.
PubMed: 38590656
DOI: 10.3389/fonc.2024.1359069 -
Cancer Management and Research 2023Breast cancer is the most common female cancer and the sixth leading cause of death, seriously affecting the quality of life of women. Platelets, one of the fragments... (Review)
Review
Breast cancer is the most common female cancer and the sixth leading cause of death, seriously affecting the quality of life of women. Platelets, one of the fragments derived from megakaryocytes, are being increasingly investigated by tumor researchers because of their anticoagulant function. According to relevant studies, platelets, as the key source of circulating angiogenesis-related factors, can regulate tumor angiogenesis and vascular integrity, and they can also affect the tumor microenvironment, thereby facilitating the proliferation and differentiation of tumor cells. By covering or transferring normal MHC I molecules to tumor cells, platelets can protect tumor cells from being killed by the immune system and facilitate tumor cell metastasis. However, details on the mechanisms involved have remained elusive. This paper reviews and analyzes studies of the role of platelets in tumorigenesis, tumor cell proliferation, tumor metastasis, and cancer treatment to provide readers with a better understanding of the relevant studies.
PubMed: 37589033
DOI: 10.2147/CMAR.S418574 -
Molecular Cancer Dec 2023Tumor angiogenesis plays vital roles in the growth and metastasis of cancer. RNA methylation is one of the most common modifications and is widely observed in eukaryotes... (Review)
Review
Tumor angiogenesis plays vital roles in the growth and metastasis of cancer. RNA methylation is one of the most common modifications and is widely observed in eukaryotes and prokaryotes. Accumulating studies have revealed that RNA methylation affects the occurrence and development of various tumors. In recent years, RNA methylation has been shown to play an important role in regulating tumor angiogenesis. In this review, we mainly elucidate the mechanisms and functions of RNA methylation on angiogenesis and progression in several cancers. We then shed light on the role of RNA methylation-associated factors and pathways in tumor angiogenesis. Finally, we describe the role of RNA methylation as potential biomarker and novel therapeutic target.
Topics: Humans; Methylation; Neoplasms; Neovascularization, Pathologic; RNA
PubMed: 38053093
DOI: 10.1186/s12943-023-01879-8 -
Current Oncology Reports Jul 2023To summarize the mechanisms of tumor angiogenesis and resistance to antiangiogenic therapy, and the influence on tumor microenvironment. (Review)
Review
PURPOSE OF REVIEW
To summarize the mechanisms of tumor angiogenesis and resistance to antiangiogenic therapy, and the influence on tumor microenvironment.
RECENT FINDINGS
Several clinical trials have investigated the activity of anti-VEGF monoclonal antibodies and tyrosine kinase inhibitors in glioblastoma, shedding the light on their limitations in terms of disease control and survival. We have outlined the mechanisms of resistance to antiangiogenic therapy, including vessel co-option, hypoxic signaling in response to vessel destruction, modulation of glioma stem cells, and trafficking of tumor-associated macrophages in tumor microenvironment. Moreover, novel generation of antiangiogenic compounds for glioblastoma, including small interfering RNAs and nanoparticles, as a delivery vehicle, could enhance selectivity and reduce side effects of treatments. There is still a rationale for the use of antiangiogenic therapy, but a better understanding of vascular co-option, vascular mimicry, and dynamic relationships between immunosuppressive microenvironment and blood vessel destruction is crucial to develop next-generation antiangiogenic compounds.
Topics: Humans; Bevacizumab; Glioblastoma; Vascular Endothelial Growth Factor A; Brain Neoplasms; Angiogenesis Inhibitors; Neovascularization, Pathologic; Tumor Microenvironment
PubMed: 37071295
DOI: 10.1007/s11912-023-01417-1 -
Romanian Journal of Morphology and... 2023Gastric cancer (GC) is still a major health problem, being one of the leading causes of cancer-related death in the world. Although the overall incidence of GC is...
Gastric cancer (GC) is still a major health problem, being one of the leading causes of cancer-related death in the world. Although the overall incidence of GC is decreasing in the United States and Western Europe, it is still high in many countries from Asia, South America, and Eastern Europe. The process of angiogenesis or the formation of new blood vessels plays an important role in cancer progression, as it allows oxygen supply, nutrients, and factors to grow tumor cells. In our study, we found that gastric neoplasms have high vascularity, with anarchic distribution, uneven in tumor stroma, sometimes with congestion vessels and microhemorrhages. Most vessels were capillaries, with a discontinuous endothelium, poorly structured basement membrane, without junctions between endothelial cells, hyperpermeable, creating the possibility of local edema in the tumor microenvironment (TME), and also extravasation of the plasma, leukocytes and even red blood cells. Angiogenesis vessels showed a low number of pericytes, which shows that they are young vessels, both morphologically and functionally immature. Tumor cells can synthesize biochemical factors [vascular endothelial growth factor-A (VEGF-A)] that stimulate the formation of new vessels (angiogenesis) to ensure their growth and metastasis. Some connective cells (tumor-associated mast cells, tumor-associated fibroblasts) are also involved in the angiogenesis process, which stimulate the progression of tumor cells and remodel the TME.
Topics: Humans; Vascular Endothelial Growth Factor A; Stomach Neoplasms; Endothelial Cells; Neovascularization, Pathologic; Neoplasms; Tumor Microenvironment
PubMed: 37867349
DOI: 10.47162/RJME.64.3.03 -
Cancer Science Jul 2023Tumor angiogenesis plays an important role in the development of cancer as it allows the delivery of oxygen, nutrients, and growth factors as well as tumor dissemination... (Review)
Review
Tumor angiogenesis plays an important role in the development of cancer as it allows the delivery of oxygen, nutrients, and growth factors as well as tumor dissemination to distant organs. Although anti-angiogenic therapy (AAT) has been approved for treating various advanced cancers, this potential strategy has limited efficacy due to resistance over time. Therefore, there is a critical need to understand how resistance develops. Extracellular vesicles (EVs) are nano-sized membrane-bound phospholipid vesicles produced by cells. A growing body of evidence suggests that tumor cell-derived EVs (T-EVs) directly transfer their cargoes to endothelial cells (ECs) to promote tumor angiogenesis. Importantly, recent studies have reported that T-EVs may play a major role in the development of resistance to AAT. Moreover, studies have demonstrated the role of EVs from non-tumor cells in angiogenesis, although the mechanisms involved are still not completely understood. In this review, we provide a comprehensive description of the role of EVs derived from various cells, including tumor cells and non-tumor cells, in tumor angiogenesis. Moreover, from the perspective of EVs, this review summarized the role of EVs in the resistance to AAT and the mechanisms involved. Due to their role in the resistance of AAT, we here proposed potential strategies to further improve the efficacy of AAT by inhibiting T-EVs.
Topics: Humans; Endothelial Cells; Neovascularization, Pathologic; Extracellular Vesicles; Cell Communication
PubMed: 37010195
DOI: 10.1111/cas.15801 -
Molecular Therapy : the Journal of the... Jun 2023While it is experimentally supported that impaired myocardial vascularization contributes to a mismatch between myocardial oxygen demand and supply, a mechanistic basis...
While it is experimentally supported that impaired myocardial vascularization contributes to a mismatch between myocardial oxygen demand and supply, a mechanistic basis for disruption of coordinated tissue growth and angiogenesis in heart failure remains poorly understood. Silencing strategies that impair microRNA biogenesis have firmly implicated microRNAs in the regulation of angiogenesis, and individual microRNAs prove to be crucial in developmental or tumor angiogenesis. A high-throughput functional screening for the analysis of a whole-genome microRNA silencing library with regard to their phenotypic effect on endothelial cell proliferation as a key parameter, revealed several anti- and pro-proliferative microRNAs. Among those was miR-216a, a pro-angiogenic microRNA which is enriched in cardiac microvascular endothelial cells and reduced in expression under cardiac stress conditions. miR-216a null mice display dramatic cardiac phenotypes related to impaired myocardial vascularization and unbalanced autophagy and inflammation, supporting a model where microRNA regulation of microvascularization impacts the cardiac response to stress.
Topics: Animals; Mice; Endothelial Cells; Heart Failure; MicroRNAs; Myocardium; Neovascularization, Pathologic; Neovascularization, Physiologic
PubMed: 37073128
DOI: 10.1016/j.ymthe.2023.04.007 -
Frontiers in Immunology 2023Angiogenesis is a hallmark of cancer biology, and neoadjuvant therapies targeting either tumor vasculature or VEGF signaling have been developed to treat solid malignant... (Review)
Review
Angiogenesis is a hallmark of cancer biology, and neoadjuvant therapies targeting either tumor vasculature or VEGF signaling have been developed to treat solid malignant tumors. However, these therapies induce complete vascular depletion leading to hypoxic niche, drug resistance, and tumor recurrence rate or leading to impaired delivery of chemo drugs and immune cell infiltration at the tumor site. Achieving a balance between oxygenation and tumor growth inhibition requires determining vascular normalization after treatment with a low dose of antiangiogenic agents. However, monotherapy within the approved antiangiogenic agents' benefits only some tumors and their efficacy improvement could be achieved using immunotherapy and emerging nanocarriers as a clinical tool to optimize subsequent therapeutic regimens and reduce the need for a high dosage of chemo agents. More importantly, combined immunotherapies and nano-based delivery systems can prolong the normalization window while providing the advantages to address the current treatment challenges within antiangiogenic agents. This review summarizes the approved therapies targeting tumor angiogenesis, highlights the challenges and limitations of current therapies, and discusses how vascular normalization, immunotherapies, and nanomedicine could introduce the theranostic potentials to improve tumor management in future clinical settings.
Topics: Humans; Angiogenesis Inhibitors; Immunotherapy; Hypoxia; Nanomedicine; Nanoparticle Drug Delivery System
PubMed: 37727791
DOI: 10.3389/fimmu.2023.1226360