Dual‐Functional Nanodroplet for Tumor Vasculature Ultrasound Imaging and Tumor Immunosuppressive Microenvironment Remodeling DOI
Yuan Liang, Siyan Zhang, Dingyi Wang

et al.

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: July 19, 2024

Abstract Accurately evaluating tumor neoangiogenesis and conducting precise interventions toward an immune‐favorable microenvironment are of significant clinical importance. In this study, a novel nanodroplet termed as the nanodroplet‐based ultrasound contrast agent therapeutic (NDs UCA/Tx ) is designed for imaging neoangiogenesis. Briefly, NDs shell constructed from engineered CMs containing antigen, vascular endothelial growth factor receptor 1 (VEGFR1) extracellular domain 2–3, CD93 ligand multimerin 2. The core composed perfluorohexane immune adjuvant R848. After injection, found to be enriched in vasculature with high expression CD93. When triggered by ultrasound, underwent acoustic droplet vaporization generated enhanced signal. Some microbubbles exploded resultant debris (with antigen R848) together adsorbed VEGF taken up nearby cells. This cleared local normalization, also served vaccine activate response. Using syngeneic mouse model, satisfactory performance activation confirmed. Thus, multifunctional successfully developed molecular remodeling microenvironment.

Language: Английский

Targeting KRAS: from metabolic regulation to cancer treatment DOI Creative Commons
Yanyan Shi, Huiling Zheng, Tianzhen Wang

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 11, 2025

The Kirsten rat sarcoma viral oncogene homolog (KRAS) protein plays a key pathogenic role in oncogenesis, cancer progression, and metastasis. Numerous studies have explored the of metabolic alterations KRAS-driven cancers, providing scientific rationale for targeting metabolism treatment. development KRAS-specific inhibitors has also garnered considerable attention, partly due to challenge acquired treatment resistance. Here, we review reprogramming glucose, glutamine, lipids regulated by oncogenic KRAS, with an emphasis on recent insights into relationship between changes mechanisms driven KRAS mutant related advances targeted therapy. We focus inhibitor discovery strategies colorectal, pancreatic, non-small cell lung cancer, including current clinical trials. Therefore, this provides overview understanding associated mutation therapeutic strategies, aiming facilitate challenges support investigation strategies.

Language: Английский

Citations

7
Self-Cascaded Pyroptosis-STING Initiators for Catalytic Metalloimmunotherapy DOI
Qiao Yu,

Shumin Sun,

Nailin Yang

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Gasdermin (GSDM)-mediated pyroptosis involves the induction of mitochondrial damage and subsequent release DNA (mtDNA), which is anticipated to activate cGAS-STING pathway, thereby augmenting antitumor immune response. However, challenges lie in effectively triggering cancer cells subsequently enhancing activation with specificity. Herein, we developed intelligent self-cascaded pyroptosis-STING initiators cobalt fluoride (CoF2) nanocatalysts for catalytic metalloimmunotherapy. CoF2 a semiconductor structure enzyme-like activity generated substantial amount reactive oxygen species (ROS) under stimulation by endogenous H2O2 exogenous ultrasound. Importantly, discovered that Co-based nanomaterials themselves induce cells. Therefore, initially acted as inducers, caspase-1/GSDMD-dependent via Co2+ ROS, leading mtDNA release. Subsequently, were further utilized STING agonists specifically capable detecting pathway. These cascade events triggered robust response, modulating immunosuppressive tumor microenvironment into an immune-supportive state, providing favorable support therapy. This innovative strategy not only significantly impeded growth primary but also elicited response augment efficacy checkpoint inhibitors preventing distant progression. Overall, this study proposed self-cascade activating amplifying pathway specificity mediated pyroptosis, representing valuable avenue future

Language: Английский

Citations

3
Current Landscape of Cancer Immunotherapy: Harnessing the Immune Arsenal to Overcome Immune Evasion DOI Creative Commons
Ankita Mitra, Anoop Kumar, Nitin Amdare

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(5), P. 307 - 307

Published: April 28, 2024

Cancer immune evasion represents a leading hallmark of cancer, posing significant obstacle to the development successful anticancer therapies. However, landscape cancer treatment has significantly evolved, transitioning into era immunotherapy from conventional methods such as surgical resection, radiotherapy, chemotherapy, and targeted drug therapy. Immunotherapy emerged pivotal component in treatment, harnessing body’s system combat offering improved prognostic outcomes for numerous patients. The remarkable success spurred efforts enhance clinical efficacy existing agents strategies. Several immunotherapeutic approaches have received approval treatments, while others are currently preclinical trials. This review explores recent progress unraveling mechanisms evaluates effectiveness diverse strategies, including vaccines, adoptive cell therapy, antibody-based treatments. It encompasses both established treatments those under investigation, providing comprehensive overview through immunological approaches. Additionally, article emphasizes current developments, limitations, challenges immunotherapy. Furthermore, by integrating analyses resistance exploring combination strategies personalized approaches, it offers valuable insights crucial novel

Language: Английский

Citations

12
YAP1 Inhibition Induces Phenotype Switching of Cancer-Associated Fibroblasts to Tumor Suppressive in Prostate Cancer DOI Creative Commons
Hongtao Song, Tong Lü, Donghui Han

et al.

Cancer Research, Journal Year: 2024, Volume and Issue: 84(22), P. 3728 - 3742

Published: Aug. 13, 2024

Prostate cancer rarely responds to immune-checkpoint blockade (ICB) therapies. Cancer-associated fibroblasts (CAF) are critical components of the immunologically "cold" tumor microenvironment and considered a promising target enhance immunotherapy response. In this study, we aimed reveal mechanisms regulating CAF plasticity identify potential strategies switch CAFs from protumorigenic antitumor phenotypes ICB efficacy in prostate cancer. Integration four single-cell RNA sequencing datasets defined CAFs, RNA-seq, flow cytometry, organoid model demonstrated functions two subtypes. Extracellular matrix-associated (ECM-CAF) promoted collagen deposition cell progression, lymphocyte-associated (Lym-CAF) exhibited an phenotype induced infiltration activation CD8+ T cells. YAP1 activity regulated ECM-CAF phenotype, silencing switching Lym-CAFs. NF-κB p65 was core transcription factor Lym-CAF subset, inhibited nuclear translocation p65. Selective depletion ECM-CAFs vivo T-cell enhanced therapeutic effects anti-PD-1 treatment on Overall, study revealed mechanism identity highlighted strategy for altering subtype suppress growth increase sensitivity ICB. Significance: regulates cancer-associated fibroblast can be targeted that promotes extracellular matrix tumor-suppressive stimulates immunity efficacy.

Language: Английский

Citations

12
Next-generation combination approaches for immune checkpoint therapy DOI
Sangeeta Goswami, Kristen E. Pauken, Linghua Wang

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(12), P. 2186 - 2199

Published: Nov. 25, 2024

Language: Английский

Citations

12
Current trends in sensitizing immune checkpoint inhibitors for cancer treatment DOI Creative Commons
Jing Wei, Wenke Li, Pengfei Zhang

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Dec. 26, 2024

Immune checkpoint inhibitors (ICIs) have dramatically transformed the treatment landscape for various malignancies, achieving notable clinical outcomes across a wide range of indications. Despite these advances, resistance to immune blockade (ICB) remains critical challenge, characterized by variable response rates and non-durable benefits. However, growing research into complex intrinsic extrinsic characteristics tumors has advanced our understanding mechanisms behind ICI resistance, potentially improving outcomes. Additionally, robust predictive biomarkers are crucial optimizing patient selection maximizing efficacy ICBs. Recent studies emphasized that multiple rational combination strategies can overcome enhance susceptibility ICIs. These findings not only deepen tumor biology but also reveal unique action sensitizing agents, extending benefits in cancer immunotherapy. In this review, we will explore underlying ICIs, discuss significance microenvironment (TIME) biomarkers, analyze current outline alternative effectiveness including personalized

Language: Английский

Citations

12
M7G-related tumor immunity: novel insights of RNA modification and potential therapeutic targets DOI Creative Commons
Mengzhen Han,

Qibo Huang,

Xinxin Li

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(4), P. 1238 - 1255

Published: Jan. 1, 2024

RNA modifications play a pivotal role in regulating cellular biology by exerting influence over distribution features and molecular functions at the post-transcriptional level.Among these modifications, N7-methylguanosine (m7G) stands out as one of most prevalent.Over recent years, significant attention has been directed towards understanding implications m7G modification.This modification is present diverse molecules, including transfer RNAs, messenger ribosomal other noncoding RNAs.Its regulation occurs through series specific methyltransferases m7G-binding proteins.Notably, implicated various diseases, prominently across multiple cancer types.Earlier studies have elucidated significance context immune within tumor microenvironment.This comprehensive review culminates synthesis findings related to modulation cells infiltration, encompassing T cells, B innate all orchestrated modification.Furthermore, interplay between its regulatory proteins can profoundly affect efficacy adjuvant therapeutics, thereby potentially serving biomarker therapeutic target for combinatory interventions types.

Language: Английский

Citations

11
Immune checkpoint blockade resistance in lung cancer: emerging mechanisms and therapeutic opportunities DOI
Jessica Konen,

Haoyi Wu,

Don L. Gibbons

et al.

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(6), P. 520 - 536

Published: May 13, 2024

Language: Английский

Citations

9
Disulfide bond-driven nanoassembly of lipophilic epirubicin prodrugs for breast cancer therapy DOI

Haimeng Yuan,

Yao Chen, Yuting Hu

et al.

Journal of Pharmaceutical Investigation, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

Language: Английский

Citations

2
Manganese Galvanic Cells Intervene in Tumor Metabolism to Reinforce cGAS‐STING Activation for Bidirectional Synergistic Hydrogen‐Immunotherapy DOI Open Access
Nailin Yang,

Shumin Sun,

Jiachen Xu

et al.

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

Published: Jan. 7, 2025

Abstract The cGAS‐STING pathway is pivotal in initiating antitumor immunity. However, tumor metabolism, particularly glycolysis, negatively regulates the activation of pathway. Herein, Mn galvanic cells (MnG) are prepared via liquid‐phase exfoliation and situ replacement to modulate thereby enhancing for bidirectional synergistic H 2 ‐immunotherapy. obtained MnG can be etched by water, enabling efficient sustained generation gas 2+ . not only activated amplified through release but also regulated glucose metabolism inhibit expression three prime repair exonuclease (TREX2), synergistically injection into tumors resulted a robust immune response, providing favorable support therapy. Consequently, combination with checkpoint blockade therapy significant suppression both primary distant tumors. Furthermore, MnG‐lipiodol dispersion exhibited remarkable efficacy transarterial embolization (TAE)‐gas‐immunotherapy rabbit orthotopic liver model. present study underscores significance employing metal cell strategy enhanced immunotherapy, offering novel approach rational design bioactive materials augment immunotherapeutic effectiveness.

Language: Английский

Citations

1