Tumor‐Associated Macrophages Nano‐Reprogrammers Induce “Gear Effect” to Empower Glioblastoma Immunotherapy DOI Open Access
Yang Wang, Guangzhe Li,

Jianlong Su

et al.

Small, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract Glioblastoma (GBM), the most malignant brain tumor with high prevalence, remains highly resistant to existing immunotherapies due significant immunosuppression within microenvironment (TME), predominantly manipulated by M2‐phenotypic tumor‐associated macrophages (M2‐TAMs). Here in this work, an M2‐TAMs targeted nano‐reprogrammers, MG5‐S‐IMDQ, is established decorating mannose molecule as targeting moiety well toll‐like receptor (TLR) 7/8 agonist, imidazoquinoline (IMDQ) on dendrimeric nanoscaffold. MG5‐S‐IMDQ demonstrated excellent capacity of penetrating blood‐brain barrier (BBB) selectively GBM microenvironment, leading a phenotype transformation and function restoration TAMs shown heightened phagocytic activity toward cells, enhanced cytotoxic effects, improved antigen cross‐presentation capability. In meantime, induction function‐oriented “gear effect”, treatment extended its impact systemically enhancing infiltration type I conventional dendritic cells (cDC1s) into sites bolstering adaptive immune responses. sum, precisely working unique target situ, nano‐reprogrammers successfully robust network that worked synergistically combat tumors. This facile nanoplatform‐based immunomodulatory strategy, serving powerful convenient monotherapy or complementary alongside other therapies like surgery, provided deep insights for advancing translational study GBM.

Language: Английский

Cold and hot tumors: from molecular mechanisms to targeted therapy DOI Creative Commons
Bo Wu, Bo Zhang, Bowen Li

et al.

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

Published: Oct. 18, 2024

Immunotherapy has made significant strides in cancer treatment, particularly through immune checkpoint blockade (ICB), which shown notable clinical benefits across various tumor types. Despite the transformative impact of ICB treatment therapy, only a minority patients exhibit positive response to it. In with solid tumors, those who respond well typically demonstrate an active profile referred as "hot" (immune-inflamed) phenotype. On other hand, non-responsive may distinct "cold" (immune-desert) phenotype, differing from features tumors. Additionally, there is more nuanced "excluded" positioned between and categories, known type. Effective differentiation understanding intrinsic factors, characteristics, TME, external factors are critical for predicting results. It widely accepted that therapy exerts profound effect on limited efficacy against or "altered" necessitating combinations therapeutic modalities enhance cell infiltration into tissue convert tumors ones. Therefore, aligning traits this review systematically delineates respective influencing extensively discusses varied approaches drug targets based assess efficacy.

Language: Английский

Citations

68
Platinum Prodrug Nanoparticles with COX‐2 Inhibition Amplify Pyroptosis for Enhanced Chemotherapy and Immune Activation of Pancreatic Cancer DOI

Bingzheng Yu,

Yushu Wang,

Tiejun Bing

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(11)

Published: Dec. 14, 2023

Pyroptosis, an emerging mechanism of programmed cell death, holds great potential to trigger a robust antitumor immune response. Platinum-based chemotherapeutic agents can induce pyroptosis via caspase-3 activation. However, these also enhance cyclooxygenase-2 (COX-2) expression in tumor tissues, leading drug resistance and evasion pancreatic cancer significantly limiting the effectiveness chemotherapy-induced pyroptosis. Here, amphiphilic polymer (denoted as PHDT-Pt-In) containing both indomethacin (In, COX-2 inhibitor) platinum(IV) prodrug (Pt(IV)) is developed, which responsive glutathione (GSH). This self-assemble into nanoparticles Pt-In NP) that disintegrate cells due GSH responsiveness, releasing In inhibit expression, hence overcoming chemoresistance amplifying cisplatin-induced mouse model, NP growth elicit innate adaptive responses. Moreover, when combined with anti-programmed death ligand (α-PD-L1) treatment, demonstrate ability completely suppress metastatic tumors, transforming "cold tumors" "hot tumors". Overall, sustained release Pt(IV) from amplifies platinum-drug-induced long-term responses, presenting generalizable strategy for cancer.

Language: Английский

Citations

62
The role of tumor-associated macrophages in tumor immune evasion DOI Creative Commons

Ruizhe Huang,

Ting Kang, Siyu Chen

et al.

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(5)

Published: May 7, 2024

Abstract Background Tumor growth is closely linked to the activities of various cells in tumor microenvironment (TME), particularly immune cells. During progression, circulating monocytes and macrophages are recruited, altering TME accelerating growth. These adjust their functions response signals from stromal Tumor-associated (TAMs), similar M2 macrophages, key regulators TME. Methods We review origins, characteristics, TAMs within This analysis includes mechanisms through which facilitate evasion promote metastasis. Additionally, we explore potential therapeutic strategies that target TAMs. Results instrumental mediating malignant behaviors. They release cytokines inhibit effector attract additional immunosuppressive primarily T cells, inducing exhaustion directly, influencing activity indirectly cellular interactions, or suppressing checkpoints. directly involved proliferation, angiogenesis, invasion, Summary Developing innovative tumor-targeted therapies immunotherapeutic currently a promising focus oncology. Given pivotal role evasion, several approaches have been devised them. include leveraging epigenetics, metabolic reprogramming, engineering repolarize TAMs, inhibiting recruitment activity, using as drug delivery vehicles. Although some these remain distant clinical application, believe future targeting will offer significant benefits cancer patients.

Language: Английский

Citations

54
Metabolic reprogramming in the tumor microenvironment of liver cancer DOI Creative Commons
Jian Lin, Dongning Rao, Mao Zhang

et al.

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

Published: Jan. 31, 2024

The liver is essential for metabolic homeostasis. onset of cancer often accompanied by dysregulated function, leading to rearrangements. Overwhelming evidence has illustrated that cellular metabolism can, in turn, promote anabolic growth and tumor propagation a hostile microenvironment. In addition supporting continuous survival, disrupted process also creates obstacles the anticancer immune response restrains durable clinical remission following immunotherapy. this review, we elucidate communication between cells their surrounding discuss how reprogramming impacts microenvironment efficacy We describe crucial role gut-liver axis remodeling crosstalk surveillance escape, highlighting novel therapeutic opportunities.

Language: Английский

Citations

46
Lactylome Analysis Unveils Lactylation‐Dependent Mechanisms of Stemness Remodeling in the Liver Cancer Stem Cells DOI Creative Commons
Fan Feng,

Jiaqin Wu,

Qingjia Chi

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(38)

Published: Aug. 5, 2024

Lactate plays a critical role as an energy substrate, metabolite, and signaling molecule in hepatocellular carcinoma (HCC). Intracellular lactate-derived protein lysine lactylation (Kla) is identified contributor to the progression of HCC. Liver cancer stem cells (LCSCs) are believed be root cause phenotypic functional heterogeneity However, impact Kla on biological processes LCSCs remains poorly understood. Here enhanced glycolytic metabolism, lactate accumulation, elevated levels observed compared HCC cells. H3K56la was found closely associated with tumourigenesis stemness LCSCs. Notably, comprehensive examination lactylome proteome ALDOA K230/322 lactylation, which promoting Furthermore, this study demonstrated tight binding between aldolase A (ALDOA) dead box deconjugate enzyme 17 (DDX17), attenuated by ultimately enhancing regulatory function DDX17 maintaining This investigation highlights significance modulating its Targeting may offer promising therapeutic approach for treating

Language: Английский

Citations

45
The emerging role of lactate in tumor microenvironment and its clinical relevance DOI

Sihan Chen,

Yining Xu, Wei Zhuo

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 590, P. 216837 - 216837

Published: March 26, 2024

Language: Английский

Citations

34
Novel tumor-associated macrophage populations and subpopulations by single cell RNA sequencing DOI Creative Commons
Juanjuan Wang,

Ningning Zhu,

Lei Su

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 29, 2024

Tumor-associated macrophages (TAMs) are present in almost all solid tumor tissues. 16They play critical roles immune regulation, angiogenesis, stem cell activation, invasion and metastasis, resistance to therapy. However, it is unclear how TAMs perform these functions. With the application of single-cell RNA sequencing (scRNA-seq), has become possible identify TAM subpopulations associated with distinct In this review, we discuss four novel tumors based on core gene signatures by scRNA-seq, including FCN1 + , SPP1 C1Q CCL18 TAMs. Functional enrichment expression scRNA-seq data from different tissues found that may induce inflammation; potentially involved cancer whereas participate regulation suppression; And cells terminal immunosuppressive not only have a stronger function but also enhance metastasis. can be further divided into populations Meanwhile, will emerging evidence highlighting separating macrophage there exist potential disconnects between types identified their actual function.

Language: Английский

Citations

25
Acidosis activates breast cancer ferroptosis through ZFAND5/SLC3A2 signaling axis and elicits M1 macrophage polarization DOI
Hanchu Xiong,

Yanan Zhai,

Yimei Meng

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 587, P. 216732 - 216732

Published: Feb. 14, 2024

Language: Английский

Citations

24
Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets DOI Creative Commons

Fan Guan,

Ruixuan Wang,

Zhenjie Yi

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Abstract Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in defense, surveillance, and homeostasis. This review systematically discusses types of hematopoietic progenitors that give rise macrophages, including primitive progenitors, erythro-myeloid stem cells. These have distinct genetic backgrounds developmental processes. Accordingly, macrophages exhibit complex diverse functions body, phagocytosis clearance cellular debris, antigen presentation, response, regulation inflammation cytokine production, tissue remodeling repair, multi-level regulatory signaling pathways/crosstalk involved homeostasis physiology. Besides, tumor-associated a key component TME, exhibiting both anti-tumor pro-tumor properties. Furthermore, functional status is closely linked development various diseases, cancer, autoimmune disorders, cardiovascular disease, neurodegenerative metabolic conditions, trauma. Targeting has emerged as promising therapeutic strategy these contexts. Clinical trials macrophage-based targeted drugs, immunotherapies, nanoparticle-based therapy were comprehensively summarized. Potential challenges future directions targeting also been discussed. Overall, our highlights significance this versatile cell human health which expected inform research clinical practice.

Language: Английский

Citations

8
Advanced Polymeric Nanoparticles for Cancer Immunotherapy: Materials Engineering, Immunotherapeutic Mechanism and Clinical Translation DOI Open Access

Wencong Jia,

Ye Wu, Yujie Xie

et al.

Advanced Materials, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract Cancer immunotherapy, which leverages immune system components to treat malignancies, has emerged as a cornerstone of contemporary therapeutic strategies. Yet, critical concerns about the efficacy and safety cancer immunotherapies remain formidable. Nanotechnology, especially polymeric nanoparticles (PNPs), offers unparalleled flexibility in manipulation‐from chemical composition physical properties precision control nanoassemblies. PNPs provide an optimal platform amplify potency minimize systematic toxicity broad spectrum immunotherapeutic modalities. In this comprehensive review, basics polymer chemistry, state‐of‐the‐art designs from physicochemical standpoint for encompassing vaccines, situ vaccination, adoptive T‐cell therapies, tumor‐infiltrating cell‐targeted antibodies, cytokine therapies are delineated. Each immunotherapy necessitates distinctively tailored design strategies nanoplatforms. The extensive applications PNPs, investigation their mechanisms action enhanced particularly focused on. profiles clinical research progress discussed. Additionally, forthcoming developments emergent trends nano‐immunotherapeutics poised transform treatment paradigms into clinics explored.

Language: Английский

Citations

6