Turning cold tumors into hot tumors by improving T-cell infiltration

Theranostics, Journal Year: 2021, Volume and Issue: 11(11), P. 5365 - 5386

Published: Jan. 1, 2021

Immunotherapy, represented by immune checkpoint inhibitors (ICIs), has greatly improved the clinical efficacy of malignant tumor therapy. ICI-mediated antitumor responses depend on infiltration T cells capable recognizing and killing cells. ICIs are not effective in "cold tumors", which characterized lack T-cell infiltration. To realize full potential immunotherapy solve this obstacle, it is essential to understand drivers into tumors. We present a critical review our understanding mechanisms underlying including impaired priming deficient homing beds. "Hot tumors" with significant associated better ICI efficacy. In review, we summarize multiple strategies that promote transformation "hot discuss these lead increased Finally, application nanomaterials provide an outlook future emerging field. The combination nanomedicines enhances cross-presentation antigens promotes A deeper opens new possibilities for development cell-based therapies improve effectiveness.

Language: Английский

---

Manganese‐Based Tumor Immunotherapy

Advanced Materials, Journal Year: 2022, Volume and Issue: 35(19)

Published: Sept. 19, 2022

Abstract As an essential micronutrient, manganese (Mn) participates in various physiological processes and plays important roles host immune system, hematopoiesis, endocrine function, oxidative stress regulation. Mn‐based nanoparticles are considered to be biocompatible show versatile applications nanomedicine, particular utilized tumor immunotherapy the following ways: 1) acting as a nanocarrier deliver immunotherapeutic agents for immunotherapy; 2) serving adjuvant regulate microenvironment enhance 3) activating host's system through cGAS‐STING pathway trigger 4) real‐time monitoring effect by magnetic resonance imaging (MRI) since Mn 2+ ions ideal MRI contrast agent which can significantly T 1 ‐weighted signal after binding proteins. This comprehensive review focuses on most recent progress of nanoplatforms immunotherapy. The characteristics first discussed guide design multifunctional nanoplatforms. Then biomedical nanoplatforms, including alone, immunotherapy‐involved multimodal synergistic therapy, imaging‐guided detail. Finally, challenges future developments highlighted.

Language: Английский

---

Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: April 2, 2024

Abstract Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, immune cells, plays a crucial role response modulation. Nanoparticles, engineered to reshape TME, shown promising results enhancing by facilitating targeted These nanoparticles can suppress fibroblast activation, promote M1 macrophage polarization, aid dendritic cell maturation, encourage T infiltration. Biomimetic further enhance increasing internalization agents cells such as cells. Moreover, exosomes, whether naturally secreted body or bioengineered, been explored regulate TME immune-related affect cancer immunotherapy. Stimuli-responsive nanocarriers, activated pH, redox, light conditions, exhibit potential accelerate co-application with checkpoint inhibitors is an emerging strategy boost anti-tumor immunity. With their ability induce long-term immunity, nanoarchitectures are structures development. This review underscores critical overcoming current driving advancement modification.

Language: Английский

---

Multifunctional mesoporous silica nanoparticles for biomedical applications

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Nov. 24, 2023

Abstract Mesoporous silica nanoparticles (MSNs) are recognized as a prime example of nanotechnology applied in the biomedical field, due to their easily tunable structure and composition, diverse surface functionalization properties, excellent biocompatibility. Over past two decades, researchers have developed wide variety MSNs-based nanoplatforms through careful design controlled preparation techniques, demonstrating adaptability various application scenarios. With continuous breakthroughs MSNs fields biosensing, disease diagnosis treatment, tissue engineering, etc., gradually moving from basic research clinical trials. In this review, we provide detailed summary beginning with comprehensive overview development history. We then discuss types nanostructured architectures, well classification nanocomposites according elements existed inorganic functional components. Subsequently, summarize primary purposes surface-functionalized modifications MSNs. following, applications MSNs, highlight targeted therapeutic modalities currently developed. Given importance translation, also progress Finally, take perspective on future direction remaining challenges field.

Language: Английский

---

Reprogramming of glutamine metabolism and its impact on immune response in the tumor microenvironment

Cell Communication and Signaling, Journal Year: 2022, Volume and Issue: 20(1)

Published: July 27, 2022

Abstract Metabolic reprogramming and immune escape play a major role in tumorigenesis. Increasing number of studies have shown that glutamine metabolism is putative determinant the anti-tumor response tumor microenvironment (TME). Usually, predatory uptake by cells TME results limited utilization affects response. The cell-programmed partitioning also However, tumors modulates regulating PD-L1 expression. Likewise, their function. Additionally, different types inhibitors extensively regulate while suppressing cell proliferation. Herein, we discuss how metabolic regulates responses, as well functional changes context targeting metabolism, which can better explain potential combination with immunotherapy for cancer.

Language: Английский

---

Drug repurposing for cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: April 18, 2024

Abstract Cancer, a complex and multifactorial disease, presents significant challenge to global health. Despite advances in surgical, radiotherapeutic immunological approaches, which have improved cancer treatment outcomes, drug therapy continues serve as key therapeutic strategy. However, the clinical efficacy of is often constrained by resistance severe toxic side effects, thus there remains critical need develop novel therapeutics. One promising strategy that has received widespread attention recent years repurposing: identification new applications for existing, clinically approved drugs. Drug repurposing possesses several inherent advantages context since repurposed drugs are typically cost-effective, proven be safe, can significantly expedite development process due their already established safety profiles. In light this, present review offers comprehensive overview various methods employed repurposing, specifically focusing on treat cancer. We describe antitumor properties candidate drugs, discuss detail how they target both hallmarks tumor cells surrounding microenvironment. addition, we examine innovative integrating with nanotechnology enhance topical delivery. also emphasize role play when used part combination regimen. To conclude, outline challenges associated consider future prospects these transitioning into application.

Language: Английский

---

Lactic acid in macrophage polarization: The significant role in inflammation and cancer

International Reviews of Immunology, Journal Year: 2021, Volume and Issue: 41(1), P. 4 - 18

Published: July 25, 2021

Metabolite lactic acid has always been regarded as a metabolic by-product rather than bioactive molecule. Recently, this view changed since it was discovered that can be used signal molecule and novel transduction functions both intracellular extracellular, which regulate key in the immune system. In recent years, more evidence shown is closely related to metabolism polarization of macrophages. During inflammation, regulator macrophage metabolism, prevent excessive inflammatory responses; malignant tumors, produced by tumor tissues promotes tumor-associated macrophages, turn progression. review, we examined relationship between metabolism. We further discussed how plays role maintaining homeostasis well biology M1/M2 imbalance human diseases. Potential methods target treatment inflammation cancer will also so provide new strategies for

Language: Английский

---

Metabolic modulation of immune checkpoints and novel therapeutic strategies in cancer

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 86, P. 542 - 565

Published: Feb. 10, 2022

Cytotoxic T-lymphocyte–associated antigen-4 (CTLA-4) or programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1)–based immune checkpoint inhibitors (ICIs) have led to significant improvements in the overall survival of patients with certain cancers and are expected benefit by achieving complete, long-lasting remissions cure. However, some who receive ICIs either fail treatment eventually develop immunotherapy resistance. The existence such necessitates a deeper understanding cancer progression, specifically nutrient regulation tumor microenvironment (TME), which includes both metabolic cross-talk between metabolites cells, intracellular metabolism cells. Here we review features behaviors TME discuss recently identified major checkpoints. We comprehensively systematically summarize modulation immunity checkpoints TME, including glycolysis, amino acid metabolism, lipid other pathways, further potential metabolism-based therapeutic strategies tested preclinical clinical settings. These findings will help determine link crosstalk immunotherapy, provide an important insight into research.

Language: Английский

---

Tumor acidity: From hallmark of cancer to target of treatment

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Aug. 29, 2022

Tumor acidity is one of the cancer hallmarks and associated with metabolic reprogramming use glycolysis, which results in a high intracellular lactic acid concentration. Cancer cells avoid stress major by activation expression proton lactate transporters exchangers have an inverted pH gradient (extracellular pHs are alkaline, respectively). The shift tumor acid-base balance promotes proliferation, apoptosis avoidance, invasiveness, metastatic potential, aggressiveness, immune evasion, treatment resistance. For example, weak-base chemotherapeutic agents may substantially reduced cellular uptake capacity due to "ion trapping". Lactic negatively affects functions activated effector T cells, stimulates regulatory them express programmed cell death receptor 1. On other hand, inversion could be weakness that will allow development new promising therapies, such as tumor-targeted pH-sensitive antibodies pH-responsible nanoparticle conjugates anticancer drugs. regulation levels pharmacological inhibition proteins (monocarboxylate transporters, H

Language: Английский

---

Obstacles for T-lymphocytes in the tumour microenvironment: Therapeutic challenges, advances and opportunities beyond immune checkpoint

EBioMedicine, Journal Year: 2022, Volume and Issue: 83, P. 104216 - 104216

Published: Aug. 17, 2022

The tumour microenvironment (TME) imposes a major obstacle to infiltrating T-lymphocytes and suppresses their function. Several immune checkpoint proteins that interfere with ligand/receptor interactions impede T-cell anti-tumour responses have been identified. Immunotherapies block checkpoints revolutionized the treatment paradigm for many patients advanced-stage tumours. However, metabolic constraints soluble factors exist within TME exacerbate functional exhaustion of tumour-infiltrating T-cells. Here we review these multifactorial mechanisms - elevated immunosuppressive metabolites enzymes, nutrient insufficiency, hypoxia, increased acidity, immense amounts extracellular ATP adenosine, dysregulated bioenergetic purinergic signalling, ionic imbalance operate in collectively suppress We discuss how scientific advances could help overcome complex obstacles T-lymphocytes, aiming stimulate further research developing new therapeutic strategies by harnessing full potential system combating cancer.

Language: Английский

---