Combining High-Z Sensitized Radiotherapy with CD73 Blockade to Boost Tumor Immunotherapy DOI
Qian Chen, Jing Chen, Qingqing Zhang

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(13), P. 12087 - 12100

Published: June 16, 2023

Radiation therapy (RT) has the capacity to induce immunogenic death in tumor cells, thereby potentially inducing situ vaccination (ISV) prime systemic antitumor immune responses. However, RT alone is often faced with various limitations during ISV induction, such as insufficient X-ray deposition and an immunosuppressive microenvironment. To overcome these limitations, we constructed nanoscale coordination particles AmGd-NPs by self-assembling high-Z metal gadolinium (Gd) small molecular CD73 inhibitor AmPCP. Then, could synergize enhance cell death, improve phagocytosis, promote antigen presentation. Additionally, also gradually release AmPCP inhibit CD73's enzymatic activity prevent conversion of extracellular ATP adenosine (Ado), driving a proinflammatory microenvironment that promotes DC maturation. As result, sensitized induced potent boosted CD8+ T cell-dependent responses against both primary metastatic tumors, which be potentiated checkpoint inhibitory therapy.

Language: Английский

Crosstalk between glucose metabolism, lactate production and immune response modulation DOI
Lei Ye, Yi Jiang, Mingming Zhang

et al.

Cytokine & Growth Factor Reviews, Journal Year: 2022, Volume and Issue: 68, P. 81 - 92

Published: Nov. 7, 2022

Language: Английский

Citations

147
TGF-β signaling in the tumor metabolic microenvironment and targeted therapies DOI Creative Commons

Xueke Shi,

Jin Yang, Shuzhi Deng

et al.

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Sept. 17, 2022

Abstract Transforming growth factor-β (TGF-β) signaling has a paradoxical role in cancer progression, and it acts as tumor suppressor the early stages but promoter late of cancer. Once cells are generated, TGF-β is responsible for orchestration immunosuppressive microenvironment (TME) supports growth, invasion, metastasis, recurrence, therapy resistance. These progressive behaviors driven by an “engine” metabolic reprogramming Recent studies have revealed that regulates driver (TMME). Intriguingly, ligands act “endocrine” cytokine influence host metabolism. Therefore, having insight into TMME instrumental acknowledging its wide range effects designing new treatment strategies. Herein, we try to illustrate concise definition based on published literature. Then, review elaborate contribution rewiring at cellular (intracellular), tissular (intercellular), organismal (cancer-host) levels. Furthermore, propose three potential applications targeting TGF-β-dependent mechanism reprogramming, paving way TGF-β-related antitumor from perspective

Language: Английский

Citations

112
Metabolic modulation of immune checkpoints and novel therapeutic strategies in cancer DOI Creative Commons
Yi Wang,

Yuya Wang,

Yifei Ren

et al.

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

Citations

104
The significance of glycolysis in tumor progression and its relationship with the tumor microenvironment DOI Creative Commons

Daoying Zhou,

Zhen Duan,

Zhenyu Li

et al.

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Dec. 14, 2022

It is well known that tumor cells rely mainly on aerobic glycolysis for energy production even in the presence of oxygen, and a modulator tumorigenesis development. The microenvironment (TME) composed cells, various immune cytokines, extracellular matrix, among other factors, complex niche supporting survival development through which they interact co-evolve with cells. In recent years, there has been renewed interest TME. Many studies have found promotes growth, metastasis, chemoresistance, as inhibiting apoptosis addition, lactic acid, metabolite glycolysis, can also accumulate TME, leading to reduced pH immunosuppression, affecting This review discusses significance development, its association potential glycolysis-targeted therapies, provide new ideas clinical treatment tumors.

Language: Английский

Citations

89
Tissue-specific abundance of interferon-gamma drives regulatory T cells to restrain DC1-mediated priming of cytotoxic T cells against lung cancer DOI Creative Commons
Maria Zagorulya, Leon Yim, Duncan M. Morgan

et al.

Immunity, Journal Year: 2023, Volume and Issue: 56(2), P. 386 - 405.e10

Published: Feb. 1, 2023

Language: Английский

Citations

88
The role of lipid metabolic reprogramming in tumor microenvironment DOI Creative Commons
Kai Yang, Xiaokun Wang, Chenghu Song

et al.

Theranostics, Journal Year: 2023, Volume and Issue: 13(6), P. 1774 - 1808

Published: Jan. 1, 2023

Metabolic reprogramming is one of the most important hallmarks malignant tumors.Specifically, lipid metabolic has marked impacts on cancer progression and therapeutic response by remodeling tumor microenvironment (TME).In past few decades, immunotherapy revolutionized treatment landscape for advanced cancers.Lipid plays pivotal role in regulating immune to immunotherapy.Here, we systematically reviewed characteristics, mechanism, cells TME, appraised effects various cell death modes (specifically ferroptosis) metabolism, summarized antitumor therapies targeting metabolism.Overall, profound microenvironment; therefore, may lead development innovative clinical applications including sensitizing immunotherapy.

Language: Английский

Citations

74
Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential DOI Creative Commons

Yu-Ling Xiao,

Yue Gong,

Ying-Jia Qi

et al.

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

Published: March 11, 2024

Abstract Diet, serving as a vital source of nutrients, exerts profound influence on human health and disease progression. Recently, dietary interventions have emerged promising adjunctive treatment strategies not only for cancer but also neurodegenerative diseases, autoimmune cardiovascular metabolic disorders. These demonstrated substantial potential in modulating metabolism, trajectory, therapeutic responses. Metabolic reprogramming is hallmark malignant progression, deeper understanding this phenomenon tumors its effects immune regulation significant challenge that impedes eradication. Dietary intake, key environmental factor, can tumor metabolism. Emerging evidence indicates might affect the nutrient availability tumors, thereby increasing efficacy treatments. However, intricate interplay between pathogenesis other diseases complex. Despite encouraging results, mechanisms underlying diet-based remain largely unexplored, often resulting underutilization management. In review, we aim to illuminate various interventions, including calorie restriction, fasting-mimicking diet, ketogenic protein restriction high-salt high-fat high-fiber aforementioned diseases. We explore multifaceted impacts these encompassing their immunomodulatory effects, biological impacts, molecular mechanisms. This review offers valuable insights into application therapies

Language: Английский

Citations

67
Advances in dendritic cell vaccination therapy of cancer DOI Open Access
Sajad Najafi, Keywan Mortezaee

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 164, P. 114954 - 114954

Published: May 29, 2023

Traditionally, vaccines have helped eradication of several infectious diseases and also saved millions lives in the human history. Those prophylactic acted through inducing immune responses against a live attenuated, killed organism or antigenic subunits to protect recipient real infection caused by pathogenic microorganism. Nevertheless, development anticancer as valuable targets health has faced challenges requires further optimizations. Dendritic cells (DCs) are most potent antigen presenting (APCs) that play essential roles tumor immunotherapies induction CD8+ T cell immunity. Accordingly, various strategies been tested employ DCs therapeutic for exploiting their activity cells. Application whole purified/recombinant peptides common approaches pulsing DCs, which then injected back into patients. Although some hopeful results reported number DC animal clinical trials cancer patients, such still inefficient require optimization. Failure vaccination is postulated due immunosuppressive microenvironment (TME), overexpression checkpoint proteins, suboptimal avidity tumor-associated (TAA)-specific lymphocytes, lack appropriate adjuvants. In this review, we an overview current experiments evaluated efficacy well focusing on improve potential including combination therapy with inhibitors (ICIs).

Language: Английский

Citations

54
Glycolysis drives STING signaling to facilitate dendritic cell antitumor function DOI Creative Commons
Zhilin Hu, Xiaoyan Yu, Rui Ding

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(7)

Published: Feb. 23, 2023

Activation of STING signaling in DCs promotes antitumor immunity. Aerobic glycolysis is a metabolic hallmark activated DCs, but how the glycolytic pathway intersects with tumor-infiltrating remains elusive. Here, we show that drives to facilitate DC-mediated immune responses. Tumor-infiltrating exhibited elevated glycolysis, and blockade by DC-specific Ldha/Ldhb double deletion resulted defective Mechanistically, augmented ATP production boost activation STING-dependent DC functions. Moreover, DC-intrinsic accelerated HIF-1α-mediated established positive feedback loop. Importantly, facilitated activity tissue samples from patients non-small cell lung cancer. Our results provide mechanistic insight into crosstalk metabolism enhances can be harnessed improve cancer therapies.

Language: Английский

Citations

44
Metabolic reprogramming in tumor immune microenvironment: Impact on immune cell function and therapeutic implications DOI Creative Commons
Yuqiang Liu,

Yu Zhao,

Huisheng Song

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 597, P. 217076 - 217076

Published: June 19, 2024

Understanding of the metabolic reprogramming has revolutionized our insights into tumor progression and potential treatment. This review concentrates on aberrant pathways in cancer cells within microenvironment (TME). Cancer differ from normal their processing glucose, amino acids, lipids order to adapt heightened biosynthetic energy needs. These shifts, which crucially alter lactic acid, acid lipid metabolism, affect not only cell proliferation but also TME dynamics. explores various immune TME. From a therapeutic standpoint, targeting these alterations represents novel treatment strategy. discusses approaches regulation metabolism different nutrients influencing enhance response. In summary, this summarizes its as target for innovative strategies, offering fresh perspectives

Language: Английский

Citations

24