Tumor Microenvironment Modulation by Cancer-Derived Extracellular Vesicles DOI Creative Commons
Artem Ten, Vadim Kumeiko, Vladislav M. Farniev

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(8), P. 682 - 682

Published: April 15, 2024

The tumor microenvironment (TME) plays an important role in the process of tumorigenesis, regulating growth, metabolism, proliferation, and invasion cancer cells, as well contributing to resistance conventional chemoradiotherapies. Several types cells with relatively stable phenotypes have been identified within TME, including cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), neutrophils, natural killer (NK) which shown modulate cell metastasis, interaction immune system, thus promoting heterogeneity. Growing evidence suggests that tumor-cell-derived extracellular vesicles (EVs), via transfer various molecules (e.g., RNA, proteins, peptides, lipids), play a pivotal transformation normal TME into their protumorigenic counterparts. This review article focuses on functions EVs modulation view how exosomes contribute importance for diagnosis therapy.

Language: Английский

Multifunctional Nanoparticle-Loaded Injectable Alginate Hydrogels with Deep Tumor Penetration for Enhanced Chemo-Immunotherapy of Cancer DOI

Xinyu Yang,

Chenlu Huang, Hanyong Wang

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(28), P. 18604 - 18621

Published: July 2, 2024

Chemo-immunotherapy has become a promising strategy for cancer treatment. However, the inability of drugs to penetrate deeply into tumor and form potent vaccines in vivo severely restricts antitumor effect chemo-immunotherapy. In this work, an injectable sodium alginate platform is reported promote penetration chemotherapeutic doxorubicin (DOX) delivery personalized vaccines. The multifunctional cross-links rapidly presence physiological concentrations Ca2+, forming hydrogel that acts as drug depot releases loaded hyaluronidase (HAase), DOX, micelles (IP-NPs) slowly sustainedly. By degrading hyaluronic acid (HA) overexpressed tissue, HAase can make tissue "loose" favor other components deeply. DOX induces immunogenic cell death (ICD) produces tumor-associated antigens (TAAs), which could be effectively captured by polyethylenimine (PEI) coated IP-NPs efficaciously facilitate maturation dendritic cells (DCs) activation T lymphocytes, thus producing long-term immune memory. Imiquimod (IMQ) core further activate system trigger more robust effect. Hence, research proposes effective treatment colorectal cancer.

Language: Английский

Citations

19
Exploring the immuno-nano nexus: A paradigm shift in tumor vaccines DOI Open Access
Yuanyuan Li, Yuxing Xu,

Wenwen Su

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 184, P. 117897 - 117897

Published: Feb. 7, 2025

Language: Английский

Citations

2
Hydrogel-guided strategies to stimulate an effective immune response for vaccine-based cancer immunotherapy DOI Creative Commons
Lei Lei, Dennis Huang, Huile Gao

et al.

Science Advances, Journal Year: 2022, Volume and Issue: 8(47)

Published: Nov. 23, 2022

Cancer vaccines have attracted widespread interest in tumor therapy because of the potential to induce an effective antitumor immune response. However, many challenges including weak immunogenicity, off-target effects, and immunosuppressive microenvironments prevented their broad clinical translation. To overcome these difficulties, delivery systems been designed for cancer vaccines. As carriers vaccine systems, hydrogels gained substantial attention they can encapsulate a variety antigens/immunomodulators protect them from degradation. This enables simultaneously reverse immunosuppression stimulate Meanwhile, controlled release properties allow precise temporal spatial loads situ further enhance response Therefore, this review summarizes classification vaccines, highlights strategies hydrogel-based provides some insights into future development

Language: Английский

Citations

69
Adaptive antitumor immune response stimulated by bio-nanoparticle based vaccine and checkpoint blockade DOI Creative Commons
Xuewei Bai, Yanmei Zhou, Yuki Yokota

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: April 8, 2022

Abstract Background Interactions between tumor and microenvironment determine individual response to immunotherapy. Triple negative breast cancer (TNBC) hepatocellular carcinoma (HCC) have exhibited suboptimal responses immune checkpoint inhibitors (ICIs). Aspartate β-hydroxylase (ASPH), an oncofetal protein associated antigen (TAA), is a potential target for Methods Subcutaneous HCC orthotopic TNBC murine models were established in immunocompetent BALB/c mice with injection of BNL-T3 4 T1 cells, respectively. Immunohistochemistry, immunofluorescence, H&E, flow cytometry, ELISA vitro cytotoxicity assays performed. Results The ASPH-MYC signaling cascade upregulates PD-L1 expression on liver cells. A bio-nanoparticle based λ phage vaccine targeting ASPH was administrated harboring syngeneic or tumors, either alone combination PD-1 blockade. In control, autocrine chemokine ligand 13 (CXCL13)-C-X-C receptor type 5 (CXCR5) axis promoted development progression TNBC. + cells T resulted cell exhaustion apoptosis, causing evasion contrast, therapy (Vaccine+PD-1 inhibitor) significantly suppressed primary hepatic mammary growth (with distant pulmonary metastases TNBC). Adaptive attributed expansion activated CD4 helper 1 (Th1)/CD8 cytotoxic (CTLs) that displayed enhanced effector functions, maturation plasma secreted high titers ASPH-specific antibody. Combination reduced infiltration immunosuppressive /CD25 /FOXP3 Tregs. When the PD-1/PD-L1 signal inhibited, CXCL13 produced by recruited CXCR5 /CD8 lymphocytes tertiary lymphoid structures (TLSs), comprising memory CTLs, follicular B germinal center, dendritic TLSs facilitate activation DCs actively recruit subsets microenvironment. These CTLs more lyse Upon treatment, formation predicts sensitivity ICI substantially prolonged overall survival Conclusions Synergistic antitumor efficacy attributable specifically ASPH, ideal TAA, combined ICIs, inhibits HCC.

Language: Английский

Citations

47
Nanomedicine embraces cancer radio-immunotherapy: mechanism, design, recent advances, and clinical translation DOI
Haonan Li, Qiang Luo, Hu Zhang

et al.

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 52(1), P. 47 - 96

Published: Nov. 25, 2022

This review overviews the landscape of nanomedicine-aided cancer radio-immunotherapy in a “from bench to clinic” manner.

Language: Английский

Citations

47
Targeting stromal cell sialylation reverses T cell-mediated immunosuppression in the tumor microenvironment DOI Creative Commons

Hannah Egan,

Oliver Treacy, Kevin Lynch

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(5), P. 112475 - 112475

Published: May 1, 2023

Immunosuppressive tumor microenvironments (TMEs) reduce the effectiveness of immune responses in cancer. Mesenchymal stromal cells (MSCs), precursors to cancer-associated fibroblasts (CAFs), promote progression by enhancing cell suppression colorectal cancer (CRC). Hyper-sialylation glycans promotes evasion through binding sialic acids their receptors, Siglecs, expressed on cells, which results inhibition effector functions. The role sialylation shaping MSC/CAF immunosuppression TME is not well characterized. In this study, we show that tumor-conditioned have increased sialyltransferase expression, α2,3/6-linked acid, and Siglec ligands. Tumor-conditioned CAFs induce exhausted immunomodulatory CD8+ PD1+ Siglec-7+/Siglec-9+ T phenotypes. vivo, targeting reverses cell-mediated immunosuppression, as shown infiltration CD25 granzyme B-expressing draining lymph node. Targeting may overcome CRC TME.

Language: Английский

Citations

42
BACH1-induced ferroptosis drives lymphatic metastasis by repressing the biosynthesis of monounsaturated fatty acids DOI Creative Commons

Xiufeng Xie,

Lusong Tian,

Yan Zhao

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 20, 2023

Esophageal squamous cell carcinoma (ESCC) is one of the fatal malignancies worldwide. It has an increased propensity to metastasize via lymphogenous routes in early stage. The prognosis patients with lymph node metastases (LNM) often worse than that without metastases. Although several factors have been found influence metastasis, mechanisms preference for specific metastatic remain poorly understood. Herein, we provide evidence intrinsic hypersensitivity tumor cells ferroptosis may proactively drive lymphatic metastasis. Serum autoantibodies associated LNM ESCC were screened using a whole-proteome protein array containing 19 394 human recombinant proteins, and anti-BACH1 autoantibody was first identified. Pan-cancer analysis ferroptosis-related genes preferential metastasis hematogenous based on Cancer Genome Atlas data performed. Only BACH1 showed significant overexpression tumors whereas it downregulated most nonlymphatic In addition, serum levels against elevated early-stage LNM. Interestingly, induction promoted but inhibited mouse models. Transcriptomic lipidomic analyses repressed SCD1-mediated biosynthesis monounsaturated fatty acids, especially oleic acid (OA). OA significantly attenuated ferroptotic phenotypes reversed properties BACH1-overexpressing cells. addition rescued Importantly, concentration gradient between primary lesions resulted chemoattraction promote invasion, thus facilitating BACH1-induced drives BACH1-SCD1-OA axis. More importantly, this study confirms double-edged sword tumorigenesis progression. clinical application ferroptosis-associated agents requires great caution.

Language: Английский

Citations

32
Cancer cell plasticity and MHC-II–mediated immune tolerance promote breast cancer metastasis to lymph nodes DOI Creative Commons
Pin‐Ji Lei, Ethel R. Pereira, Patrik Andersson

et al.

The Journal of Experimental Medicine, Journal Year: 2023, Volume and Issue: 220(9)

Published: June 21, 2023

Tumor-draining lymph nodes (TDLNs) are important for tumor antigen–specific T cell generation and effective anticancer immune responses. However, TDLNs often the primary site of metastasis, causing suppression worse outcomes. Through cross-species single-cell RNA-Seq analysis, we identified features defining cancer heterogeneity, plasticity, evasion during breast progression node metastasis (LNM). A subset cells in exhibited elevated MHC class II (MHC-II) gene expression both mice humans. MHC-II+ lacked costimulatory molecule expression, leading to regulatory (Treg) expansion fewer CD4+ effector TDLNs. Genetic knockout MHC-II reduced LNM Treg expansion, while overexpression transactivator, Ciita, worsened caused excessive expansion. These findings demonstrate that promotes

Language: Английский

Citations

32
Nanovaccine-based strategies for lymph node targeted delivery and imaging in tumor immunotherapy DOI Creative Commons
Ao He, Xiaoye Li, Zhuo Dai

et al.

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: July 23, 2023

Abstract Therapeutic tumor vaccines have attracted considerable attention in the past decade; they can induce regression, eradicate minimal residual disease, establish lasting immune memory and avoid non-specific adverse side effects. However, challenge field of therapeutic is ensuring delivery components to lymph nodes (LNs) activate cells. The clinical response rate traditional falls short expectations due inadequate node delivery. With rapid development nanotechnology, a large number nanoplatform-based LN-targeting nanovaccines been exploited for optimizing immunotherapies. In addition, some possess non-invasive visualization performance, which benefit understanding kinetics nanovaccine exposure LNs. Herein, we present parameters nanoplatforms, such as size, surface modification, shape, deformability, affect functions nanovaccines. recent advances nanoplatforms with different promoting are also summarized. Furthermore, emerging LNs-targeting nanoplatform-mediated imaging strategies both improve targeting performance enhance quality LN discussed. Finally, summarize prospects challenges /or strategies, optimize efficacy

Language: Английский

Citations

32
Mannosylated STING Agonist Drugamers for Dendritic Cell-Mediated Cancer Immunotherapy DOI Creative Commons
Dinh Chuong Nguyen, Kefan Song,

Simbarashe Jokonya

et al.

ACS Central Science, Journal Year: 2024, Volume and Issue: 10(3), P. 666 - 675

Published: Feb. 23, 2024

The Stimulator of Interferon Genes (STING) pathway is a promising target for cancer immunotherapy. Despite recent advances, therapies targeting the STING are often limited by routes administration, suboptimal activation, or off-target toxicity. Here, we report dendritic cell (DC)-targeted polymeric prodrug platform (polySTING) that designed to optimize intracellular delivery diamidobenzimidazole (diABZI) small-molecule agonist while minimizing toxicity after parenteral administration. PolySTING incorporates mannose ligands as comonomer, which facilitates its uptake in CD206+/mannose receptor+ professional antigen-presenting cells (APCs) tumor microenvironment (TME). conjugated through cathepsin B-cleavable valine-alanine (VA) linker selective drug release receptor-mediated endocytosis. When administered intravenously tumor-bearing mice, polySTING selectively targeted APCs TME, resulting increased cross-presenting CD8+ DCs, infiltrating T TME well maturation across multiple DC subtypes tumor-draining lymph node (TDLN). Systemic administration slowed growth B16-F10 murine melanoma model 4T1 breast with an acceptable safety profile. Thus, demonstrate delivers agonists systemic generating efficacious DC-driven antitumor immunity minimal side effects. This new may offer opportunities combining efficient other therapeutic strategies.

Language: Английский

Citations

15