Metformin: update on mechanisms of action and repurposing potential

Nature Reviews Endocrinology, Journal Year: 2023, Volume and Issue: 19(8), P. 460 - 476

Published: May 2, 2023

Language: Английский

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Tumor‐associated macrophages in liver cancer: From mechanisms to therapy

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(11), P. 1112 - 1140

Published: Sept. 7, 2022

Abstract Multidimensional analyses have demonstrated the presence of a unique tumor microenvironment (TME) in liver cancer. Tumor‐associated macrophages (TAMs) are among most abundant immune cells infiltrating TME and present at all stages cancer progression, targeting TAMs has become one favored immunotherapy strategies. In addition, distinct origins. At early stage cancer, can provide niche for maintenance stem cells. contrast, (CSCs) or poorly differentiated key factors modulating macrophage activation. review, we first propose origin connection between precursor Macrophages undergo dynamic phenotypic transition during carcinogenesis. this course such transition, it is critical to determine appropriate timing therapy block specific markers suppress pro‐tumoral TAMs. The review provides more detailed discussion trends surface than previous reviews. Complex crosstalk occurs play indispensable roles angiogenesis, autophagy due their heterogeneity robust plasticity. interact with other by directing cell‐to‐cell contact secreting various effector molecules. Similarly, combined drive recruitment polarization. Despite latest achievements advancements treatment strategies following studies, comprehensive discussions on communication currently lacking. discussed interactions (from cell maturation), therapeutic (including chimeric antigen receptor macrophages), clinical trials hepatocellular carcinoma (HCC) intrahepatic cholangiocarcinoma (iCCA) rationale further investigation as potential target treating patients

Language: Английский

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The Impact of the Tumor Microenvironment on Macrophage Polarization in Cancer Metastatic Progression

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(12), P. 6560 - 6560

Published: June 18, 2021

Rather than primary solid tumors, metastasis is one of the hallmarks most cancer deaths. Metastasis a multistage event in which cells escape from tumor survive circulation and disseminate to distant sites. According Stephen Paget's "Seed Soil" hypothesis, metastatic capacity determined not only by internal oncogenic driving force but also external environment cells. Throughout body, macrophages are required for maintaining tissue homeostasis, even milieu. To fulfill these multiple functions, polarized inflammation status (M1-like) anti-inflammation (M2-like) maintain balance between regeneration. However, cell-enforced tumor-associated (TAMs) (a high M2/M1 ratio status) associated with poor prognosis such as ovarian cancer. In fact, clinical evidence has verified that TAMs, representing up 50% mass, exert both protumor immunosuppressive effects promoting through secretion interleukin 10 (IL10), transforming growth factor β (TGFβ), VEGF, expression PD-1 consumption arginine inhibit T cell anti-tumor function. underlying molecular mechanisms microenvironment favors reprogramming TAMs establish premetastatic niche remain controversial. this review, we examine latest investigations during development, microenvironmental factors involved macrophage polarization, TAM-mediated metastasis. We hope dissect critical roles metastasis, potential applications TAM-targeted therapeutic strategies treatment discussed.

Language: Английский

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Reversing insufficient photothermal therapy-induced tumor relapse and metastasis by regulating cancer-associated fibroblasts

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: May 19, 2022

Abstract Insufficient tumor accumulation and distribution of photosensitizers as well low antitumor immunity severely restrict the therapeutic efficacy photothermal therapy (PTT). Cancer-associated fibroblasts (CAFs) play a key role in extracellular matrix (ECM) remodeling immune evasion. Reshaping microenvironment via CAF regulation might provide potential approach for complete elimination combination with PTT. Here, cell-derived microparticles co-delivering calcipotriol Indocyanine green (Cal/ICG@MPs) are developed to modulate CAFs improved PTT efficacy. Cal/ICG@MPs efficiently target tissues regulate reduce ECM, resulting enhanced penetration ICG generate strong activate CD8 + T cell-mediated immunity. In addition, Cal/ICG@MPs-triggered enhances infiltration cells ameliorates CAF-induced antigen-mediated activation-induced cell death tumor-specific response PTT, eliciting long-term memory inhibit recurrence metastasis. Our results support promising drug improve cancer treatment.

Language: Английский

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Tumor-Associated Macrophages Regulate PD-1/PD-L1 Immunosuppression

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

Published: May 3, 2022

Anti-programmed cell death 1 (PD-1) or anti-PD-ligand (L) drugs, as classic immune checkpoint inhibitors, are considered promising treatment strategies for tumors. In clinical practice, some cancer patients experience drug resistance and disease progression in the process of anti-PD-1/PD-L1 immunotherapy. Tumor-associated macrophages (TAMs) play key roles regulating PD-1/PD-L1 immunosuppression by inhibiting recruitment function T cells through cytokines, superficial ligands, exosomes. There several therapies available to recover anticancer efficacy inhibitors targeting TAMs, including inhibition TAM differentiation re-education activation. this review, we will summarize mechanisms TAMs blocker resistance. Furthermore, discuss that were designed deplete re-educate intervene with chemokines secreted exosomes from M1 macrophages, providing more potential options improve inhibitors.

Language: Английский

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Biomaterials tools to modulate the tumour microenvironment in immunotherapy

Nature Reviews Bioengineering, Journal Year: 2023, Volume and Issue: 1(2), P. 125 - 138

Published: Jan. 25, 2023

Language: Английский

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Metal-Phenolic Network-Enabled Lactic Acid Consumption Reverses Immunosuppressive Tumor Microenvironment for Sonodynamic Therapy

ACS Nano, Journal Year: 2021, Volume and Issue: 15(10), P. 16934 - 16945

Published: Oct. 18, 2021

Nanomedicine has revolutionized cancer therapeutic strategies but not completely changed the outcomes of tricky tumors that evolve a sophisticated immunosuppressive tumor microenvironment (TME) such as acidification. Here, metal-phenolic network-based nanocomplex embedded with lactate oxidase (LOX) and mitochondrial respiration inhibitor atovaquone (ATO) was constructed for TME remodeling sonodynamic therapy (SDT). In this nanocomplex, sonosensitizer chlorin e6-conjugated polyphenol derivative can induce generation lethal reactive oxygen species upon ultrasound irradiation. LOX served catalyst intracellular lactic acid exhaustion, ATO led to dysfunction decrease consumption. This reversed status by alleviating hypoxia acidic TME, achieving characteristic enhancement SDT inhibition proliferation metastasis.

Language: Английский

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Harnessing anti‐tumor and tumor‐tropism functions of macrophages via nanotechnology for tumor immunotherapy

Exploration, Journal Year: 2022, Volume and Issue: 2(3)

Published: Feb. 25, 2022

Reprogramming the immunosuppressive tumor microenvironment by modulating macrophages holds great promise in immunotherapy. As a class of professional phagocytes and antigen-presenting cells innate immune system, can not only directly engulf clear cells, but also play roles presenting tumor-specific antigen to initiate adaptive immunity. However, tumor-associated (TAMs) usually display tumor-supportive M2 phenotype rather than anti-tumor M1 phenotype. They support escape immunological surveillance, aggravate progression, impede T cell Although many TAMs-modulating agents have shown success therapy multiple tumors, they face enormous challenges including poor accumulation off-target side effects. An alternative solution is use advanced nanostructures, which deliver augment therapeutic efficacy, serve as modulators TAMs. Another important strategy exploitation macrophage-derived components tumor-targeting delivery vehicles. Herein, we summarize recent advances targeting engineering for immunotherapy, (1) direct indirect effects on augmentation immunotherapy (2) strategies macrophage-based drug carriers. The existing perspectives immunotherapies are highlighted.

Language: Английский

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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

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Hybrid‐Membrane‐Decorated Prussian Blue for Effective Cancer Immunotherapy via Tumor‐Associated Macrophages Polarization and Hypoxia Relief

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(14)

Published: Feb. 1, 2022

Both tumor-associated macrophages (TAMs) and hypoxia condition severely restrict the antitumor potency during cancer immunotherapy. It is essential to overcome two issues for improving therapeutic efficacy. In this study, a hollow mesoporous Prussian blue (HMPB) nanosystem with mannose decoration hydroxychloroquine (HCQ) adsorption built, form Man-HMPB/HCQ. can facilitate cellular internalization via mannose-receptor mediated endocytosis induce TAM polarization iron ion/HCQ release HMPB degradation. The hybrid macrophage thylakoid (TK) membrane camouflaged on Man-HMPB/HCQ surface, denoted as TK-M@Man-HMPB/HCQ, reduce in vivo reticuloendothelial system uptake, enhance tumor accumulation, mitigate hypoxia. results indicate that TK-M@Man-HMPB/HCQ notably inhibits growth, induces polarization, facilitates cytotoxic T lymphocytes infiltration, alleviates microenvironment. rational design may provide new pathway modulate microenvironment promoting immunotherapy effects.

Language: Английский

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