The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(3), P. 374 - 403

Published: March 1, 2023

Language: Английский

---

Therapeutic Targeting of the Tumor Microenvironment

Cancer Discovery, Journal Year: 2021, Volume and Issue: 11(4), P. 933 - 959

Published: April 1, 2021

Abstract Strategies to therapeutically target the tumor microenvironment (TME) have emerged as a promising approach for cancer treatment in recent years due critical roles of TME regulating progression and modulating response standard-of-care therapies. Here, we summarize current knowledge regarding most advanced TME-directed therapies, which either been clinically approved or are currently being evaluated trials, including immunotherapies, antiangiogenic drugs, treatments directed against cancer-associated fibroblasts extracellular matrix. We also discuss some challenges associated with future perspectives this evolving field. Significance: This review provides comprehensive analysis therapies targeting TME, combining discussion underlying basic biology clinical evaluation different therapeutic approaches, highlighting perspectives.

Language: Английский

---

Fluid transport in the brain

Physiological Reviews, Journal Year: 2021, Volume and Issue: 102(2), P. 1025 - 1151

Published: May 5, 2021

The brain harbors a unique ability to, figuratively speaking, shift its gears. During wakefulness, the is geared fully toward processing information and behaving, while homeostatic functions predominate during sleep. blood-brain barrier establishes stable environment that optimal for neuronal function, yet imposes physiological problem; transcapillary filtration forms extracellular fluid in other organs reduced to minimum brain. Consequently, depends on special [the cerebrospinal (CSF)] flushed into along perivascular spaces created by astrocytic vascular endfeet. We describe this pathway, coined term glymphatic system, based dependency endfeet their adluminal expression of aquaporin-4 water channels facing CSF-filled spaces. Glymphatic clearance potentially harmful metabolic or protein waste products, such as amyloid-β, primarily active sleep, when drivers, cardiac cycle, respiration, slow vasomotion, together efficiently propel CSF inflow periarterial brain's space contains an abundance proteoglycans hyaluronan, which provide low-resistance hydraulic conduit rapidly can expand shrink sleep-wake cycle. system brain, meets requisites maintain homeostasis similar peripheral organs, considering blood-brain-barrier paths formation egress CSF.

Language: Английский

---

The Glymphatic System: A Novel Component of Fundamental Neurobiology

Journal of Neuroscience, Journal Year: 2021, Volume and Issue: 41(37), P. 7698 - 7711

Published: Sept. 15, 2021

Throughout the body, lymphatic fluid movement supports critical functions including clearance of excess and metabolic waste. The glymphatic system is analog in CNS. As such, plays a key role regulating directional interstitial movement, waste clearance, and, potentially, brain immunity. enables bulk CSF from subarachnoid space along periarterial spaces, where it mixes with within parenchyma before ultimately exiting via perivenous spaces. This review focuses on important questions about structure this system, why needs transport unexplored aspects transport. We provide evidence that astrocytes blood vessels determine shape perivascular space, controlling fluid. Glymphatic has potential to alter local as well global signaling molecules metabolites. also highlight for cross talk among cardiovascular gastrointestinal tract, system. Much remains be studied, but we propose glymphatic/lymphatic acts cornerstone between body.

Language: Английский

---

From influenza to COVID-19: Lipid nanoparticle mRNA vaccines at the frontiers of infectious diseases

Acta Biomaterialia, Journal Year: 2021, Volume and Issue: 131, P. 16 - 40

Published: June 18, 2021

Language: Английский

---

Lymphatic Malformations: Genetics, Mechanisms and Therapeutic Strategies

Circulation Research, Journal Year: 2021, Volume and Issue: 129(1), P. 136 - 154

Published: June 24, 2021

Lymphatic vessels maintain tissue fluid homeostasis by returning to blood circulation interstitial that has extravasated from the capillaries. They provide a trafficking route for cells of immune system, thus critically contributing surveillance. Developmental or functional defects in lymphatic vessels, their obstruction damage, lead accumulation tissues, resulting lymphedema. Here we discuss developmental anomalies called malformations and complex manifest as localized multifocal lesions vasculature, respectively. are rare diseases caused mostly somatic mutations can present with variable symptoms based upon size location composed fluid-filled cisterns channels. Substantial progress been made recently understanding molecular basis pathogenesis through identification genetic causes, combined elucidation underlying mechanisms animal disease models patient-derived endothelial cells. Most solitary cause occur genes encode components oncogenic growth factor signal transduction pathways. This led successful repurposing some targeted cancer therapeutics treatment anomalies. Apart act cell-autonomous drivers these anomalies, current evidence points superimposed paracrine contribute additional targets therapeutic intervention. Here, review advances new strategies on identified

Language: Английский

---

The roles of tertiary lymphoid structures in chronic diseases

Nature Reviews Nephrology, Journal Year: 2023, Volume and Issue: 19(8), P. 525 - 537

Published: April 12, 2023

Language: Английский

---

Lymphatic vessels in bone support regeneration after injury

Cell, Journal Year: 2023, Volume and Issue: 186(2), P. 382 - 397.e24

Published: Jan. 1, 2023

Blood and lymphatic vessels form a versatile transport network provide inductive signals to regulate tissue-specific functions. in bone osteogenesis hematopoiesis, but current dogma suggests that lacks vessels. Here, by combining high-resolution light-sheet imaging cell-specific mouse genetics, we demonstrate presence of human bones. We find expand during genotoxic stress. VEGF-C/VEGFR-3 signaling stress-induced IL6 drive lymphangiogenesis During lymphangiogenesis, secretion CXCL12 from proliferating endothelial cells is critical for hematopoietic regeneration. Moreover, lymphangiocrine triggers expansion mature Myh11+ CXCR4+ pericytes, which differentiate into contribute In aged animals, such Myh11-positive response stress impaired. These data suggest as therapeutic avenue stimulate

Language: Английский

---

The Glymphatic System (En)during Inflammation

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(14), P. 7491 - 7491

Published: July 13, 2021

The glymphatic system is a fluid-transport that accesses all regions of the brain. It facilitates exchange cerebrospinal fluid and interstitial clears waste from metabolically active Astrocytic endfeet their dense expression aquaporin-4 water channels promote between perivascular spaces neuropil. Cerebrospinal fluids are together transported back to vascular compartment by meningeal cervical lymphatic vessels. Multiple lines work show neurological diseases in general impair transport. Insofar as plays pseudo-lymphatic role central nervous system, it poised play neuroinflammation. In this review, we discuss how association with vessel calls for renewal established concepts on CNS an immune-privileged site. We also potential approaches target combat

Language: Английский

---

ATP and Adenosine Metabolism in Cancer: Exploitation for Therapeutic Gain

Pharmacological Reviews, Journal Year: 2022, Volume and Issue: 74(3), P. 799 - 824

Published: June 23, 2022

Adenosine is an evolutionary ancient metabolic regulator linking energy state to physiologic processes, including immunomodulation and cell proliferation. Tumors create adenosine-rich immunosuppressive microenvironment through the increased release of ATP from dying stressed cells its ectoenzymatic conversion into adenosine. Therefore, adenosine pathway becomes important therapeutic target improve effectiveness immune therapies. Prior research has focused largely on two major ectonucleotidases, ectonucleoside triphosphate diphosphohydrolase 1/cluster differentiation (CD)39 ecto-5′-nucleotidase/CD73, which catalyze breakdown extracellular adenosine, subsequent activation different subtypes receptors with mixed findings antitumor protumor effects. New findings, needed for more effective approaches, require consideration redundant pathways controlling intratumoral levels, alternative NAD-inactivating CD38-ectonucleotide pyrophosphatase phosphodiesterase (ENPP)1-CD73 axis, counteracting ATP-regenerating pathway, cellular uptake phosphorylation by kinase. This review provides a holistic view intracellular metabolism as integrated complex network summarizes recent data underlying mechanisms precursors ADP control cancer immunosurveillance, tumor angiogenesis, lymphangiogenesis, cancer-associated thrombosis, blood flow, perfusion. Special attention given differences commonalities in purinome cancers, heterogeneity microenvironment, subcellular compartmentalization system, novel roles purine-converting enzymes targets therapy.

Significance Statement

The discovery role checkpoint led development strategies targeting signaling multiple clinical trials preclinical models. Here we identify gaps knowledge that need be filled gain agents key components and, this basis, provide network.

Language: Английский

---