Alendronate Triggered Dual‐Cascade Targeting Prodrug Nanoparticles for Enhanced Tumor Penetration and STING Activation of Osteosarcoma DOI Open Access

Meifang Shen,

Yushu Wang,

Tiejun Bing

и другие.

Advanced Functional Materials, Год журнала: 2023, Номер 33(49)

Опубликована: Сен. 3, 2023

Abstract The complex physiological environment in bone tissue poses a challenge to the efficient delivery of chemotherapeutic agents for osteosarcoma (OS) treatment; hence, an drug system designed OS is highly desired. Herein, alendronate (Ale)‐based cationic platinum prodrug nanoparticles (Ale NP) are developed, which exhibit cascade responsiveness tumor microenvironment. With Ale triggered targeting and charge reversal effects, NP demonstrates superior capacity achieving deep penetration into dense tissues. Furthermore, can induce dendritic cell (DC) maturation via activation cyclic GMP‐AMP synthase‐stimulator interferon genes (cGAS‐STING) pathway using drugs. potent phenanthridine (Pt(II)) be released presence overexpressed glutathione (GSH) cells, thereby dual‐targeted drugs OS. Notably, not only effectively eliminates internal region but also acts as STING agonist reverse suppressive microenvironment Overall, Ale‐triggered dual‐cascade significantly improve OS, hence paving promising avenue clinical treatment

Язык: Английский

Targeting DHX9 Triggers Tumor-Intrinsic Interferon Response and Replication Stress in Small Cell Lung Cancer DOI Creative Commons
Takahiko Murayama, Jun Nakayama, Xinpei Jiang

и другие.

Cancer Discovery, Год журнала: 2024, Номер 14(3), С. 468 - 491

Опубликована: Янв. 4, 2024

Abstract Activating innate immunity in cancer cells through cytoplasmic nucleic acid sensing pathways, a phenomenon known as “viral mimicry,” has emerged an effective strategy to convert immunologically “cold” tumors into “hot.” Through curated CRISPR-based screen of RNA helicases, we identified DExD/H-box helicase 9 (DHX9) potent repressor double-stranded (dsRNA) small cell lung cancers (SCLC). Depletion DHX9 induced accumulation dsRNA and triggered tumor-intrinsic immunity. Intriguingly, ablating also aberrant R-loops, which resulted increase DNA damage–derived replication stress SCLCs. In vivo, deletion promoted decrease tumor growth while inducing more immunogenic microenvironment, invigorating responsiveness immune-checkpoint blockade. These findings suggest that is crucial stress, representing promising target for SCLC other genomic instability contributes pathology. Significance: One trigger immune response within enhance immunotherapy efficacy by endogenous “virus-mimetic” accumulation. Here, identify viral-mimicry-inducing factor involved the suppression RNAs R-loops propose novel antitumor See related commentary Chiappinelli, p. 389. This article featured Selected Articles from Issue, 384

Язык: Английский

Процитировано

35
Spatiotemporal single-cell analysis decodes cellular dynamics underlying different responses to immunotherapy in colorectal cancer DOI Creative Commons
Yuqing Chen, Dongfang Wang, Yingjie Li

и другие.

Cancer Cell, Год журнала: 2024, Номер 42(7), С. 1268 - 1285.e7

Опубликована: Июль 1, 2024

Expanding the efficacy of immune checkpoint blockade (ICB) in colorectal cancer (CRC) presses for a comprehensive understanding treatment responsiveness. Here, we analyze multiple sequential single-cell samples from 22 patients undergoing PD-1 to map evolution local and systemic immunity CRC patients. In tumors, identify coordinated cellular programs exhibiting distinct response associations. Specifically, exhausted T (Tex) or tumor-reactive-like CD8+ (Ttr-like) cells are closely related efficacy, Tex show correlated proportion changes with other tumor-enriched cell types following blockade. addition, reveal less-exhausted phenotype blood-associated Ttr-like tumors find that their higher abundance suggests better outcomes. Finally, major histocompatibility complex (MHC) II-related signature circulating at baseline is linked superior responses. Our study provides insights into spatiotemporal dynamics neoadjuvant CRC.

Язык: Английский

Процитировано

33
Zinc–Iron Bimetallic Peroxides Modulate the Tumor Stromal Microenvironment and Enhance Cell Immunogenicity for Enhanced Breast Cancer Immunotherapy Therapy DOI
Yujie Lu, Youdong Chen,

Guanghui Hou

и другие.

ACS Nano, Год журнала: 2024, Номер 18(15), С. 10542 - 10556

Опубликована: Апрель 1, 2024

Immunotherapy has emerged as a potential approach for breast cancer treatment. However, the rigid stromal microenvironment and low immunogenicity of tumors strongly reduce sensitivity to immunotherapy. To sensitize patients immunotherapy, hyaluronic acid-modified zinc peroxide–iron nanocomposites (Fe-ZnO2@HA, abbreviated FZOH) were synthesized remodel increase tumor immunogenicity. The constructed FZOH spontaneously generated highly oxidative hydroxyl radicals (·OH) that degrade acid (HA) in extracellular matrix (ECM), thereby reshaping enhancing blood perfusion, drug penetration, immune cell infiltration. Furthermore, not only triggers pyroptosis through activation caspase-1/GSDMD-dependent pathway but also induces ferroptosis various mechanisms, including increasing levels Fe2+ intracellular iron pool, downregulating expression FPN1 inhibit efflux, activating p53 signaling cause failure SLC7A11-GSH-GPX4 axis. Upon treatment with FZOH, 4T1 cells undergo both pyroptosis, exhibiting strong immunogenic response. remodeling response induced by collectively compensate limitations immunotherapy significantly enhance antitumor checkpoint inhibitor αPD-1. This study proposes perspective therapy cancer.

Язык: Английский

Процитировано

32
T-cell infiltration and its regulatory mechanisms in cancers: insights at single-cell resolution DOI Creative Commons

Wenhui Yang,

Shimao Liu,

Mengyun Mao

и другие.

Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)

Опубликована: Фев. 2, 2024

Abstract Tumor-infiltrating T cells recognize, attack, and clear tumor cells, playing a central role in antitumor immune response. However, certain can impair this response help escape. Therefore, exploring the factors that influence T-cell infiltration is crucial to understand immunity improve therapeutic effect of cancer immunotherapy. The use single-cell RNA sequencing (scRNA-seq) allows high-resolution analysis precise composition with different phenotypes other microenvironmental factors, including non-immune stromal related molecules microenvironment various types. In review, we summarized research progress on crosstalk cytokines during using scRNA-seq provide insights into mechanisms regulating contribute new perspectives

Язык: Английский

Процитировано

28
A Single‐Atom Manganese Nanozyme Mn‐N/C Promotes Anti‐Tumor Immune Response via Eliciting Type I Interferon Signaling DOI Creative Commons
Wen Qiao, Jingqi Chen,

Huayuan Zhou

и другие.

Advanced Science, Год журнала: 2024, Номер 11(14)

Опубликована: Фев. 2, 2024

Tumor microenvironment (TME)-induced nanocatalytic therapy is a promising strategy for cancer treatment, but the low catalytic efficiency limits its therapeutic efficacy. Single-atom catalysts (SACs) are new type of nanozyme with incredible efficiency. Here, single-atom manganese (Mn)-N/C constructed. Mn-N/C catalyzes conversion cellular H

Язык: Английский

Процитировано

26
Overcoming cold tumors: a combination strategy of immune checkpoint inhibitors DOI Creative Commons

Peng Ouyang,

Lijuan Wang, Jianlong Wu

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Март 13, 2024

Immune Checkpoint Inhibitors (ICIs) therapy has advanced significantly in treating malignant tumors, though most 'cold' tumors show no response. This resistance mainly arises from the varied immune evasion mechanisms. Hence, understanding transformation to 'hot' is essential developing effective cancer treatments. Furthermore, tumor profiling critical, requiring a range of diagnostic techniques and biomarkers for evaluation. The success immunotherapy relies on T cells' ability recognize eliminate cells. In absence cell infiltration leads ineffectiveness ICI therapy. Addressing these challenges, especially impairment activation homing, crucial enhance therapy's efficacy. Concurrently, strategies convert into ones, including boosting adoptive therapies such as cell-recruiting bispecific antibodies Chimeric Antigen Receptor (CAR) cells, are under extensive exploration. Thus, identifying key factors that impact vital creating treatments targeting tumors.

Язык: Английский

Процитировано

20
Tumor battlefield within inflamed, excluded or desert immune phenotypes: the mechanisms and strategies DOI Creative Commons
Siwei Zheng, Wenwen Wang, Lesang Shen

и другие.

Experimental Hematology and Oncology, Год журнала: 2024, Номер 13(1)

Опубликована: Авг. 6, 2024

Abstract The tumor microenvironment demonstrates great immunophenotypic heterogeneity, which has been leveraged in traditional immune-hot/cold categorization based on the abundance of intra-tumoral immune cells. By incorporating spatial contexture, immunophenotype was further elaborated into immune-inflamed, immune-excluded, and immune-desert. However, mechanisms underlying these different phenotypes are yet to be comprehensively elucidated. In this review, we discuss how cells interact collectively shape landscape from perspectives cells, extracellular matrix, cancer metabolism, summarize potential therapeutic options according distinct immunophenotypes for personalized precision medicine.

Язык: Английский

Процитировано

19
Tertiary lymphoid structures and cancer immunotherapy: From bench to bedside DOI Creative Commons
Florent Peyraud, Jean‐Philippe Guégan, Lucile Vanhersecke

и другие.

Med, Год журнала: 2025, Номер 6(1), С. 100546 - 100546

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

5
Tumor microenvironment: recent advances in understanding and its role in modulating cancer therapies DOI
Disha D. Shah, Mehul R. Chorawala, Neha R. Raghani

и другие.

Medical Oncology, Год журнала: 2025, Номер 42(4)

Опубликована: Март 18, 2025

Язык: Английский

Процитировано

4
Radiomics signature for dynamic monitoring of tumor inflamed microenvironment and immunotherapy response prediction DOI Creative Commons
Kinga Bernatowicz, Ramon Amat, Olivia Prior

и другие.

Journal for ImmunoTherapy of Cancer, Год журнала: 2025, Номер 13(1), С. e009140 - e009140

Опубликована: Янв. 1, 2025

The efficacy of immune checkpoint inhibitors (ICIs) depends on the tumor microenvironment (TIME), with a preference for T cell-inflamed TIME. However, challenges in tissue-based assessments via biopsies have triggered exploration non-invasive alternatives, such as radiomics, to comprehensively evaluate TIME across diverse cancers. To address these challenges, we develop an ICI response signature by integrating radiomics gene-expression profiles. We conducted pan-cancer investigation into utility assessment, including 1360 tumors from 428 patients. Leveraging contrast-enhanced CT images, characterized through RNA gene expression analysis, using signature. Subsequently, CT-radiomic predicting inflamed (CT-TIME) was developed and externally validated. Machine learning employed select robust radiomic features predict study also integrated independent cohorts longitudinal baseline biopsies, comprehensive immunohistochemistry panel evaluation assess biological associations, spatiotemporal landscape clinical CT-TIME. CT-TIME signature, comprising four linked T-cell microenvironment, demonstrated performance AUCs (95% CI) 0.85 (0.73 0.96) (training) 0.78 (0.65 0.92) (external validation). scores exhibited positive correlations CD3, CD8, CD163 expression. Intrapatient analysis revealed considerable heterogeneity between tumors, which could not be assessed biopsies. Evaluation aggregated per-patient highlighted its promising dynamically assessing immunotherapy scenarios advanced cancer. Despite demonstrating progression disease at first follow-up, patients within status group, identified CT-TIME, significantly prolonged progression-free survival (PFS), some surpassing 5 months, suggesting potential phenomenon pseudoprogression. Cox models images statistically significant reduction risk PFS cohort (HR 0.62, 95% CI 0.44 0.88, p=0.007), Kaplan-Meier further confirmed substantial differences uninflamed (log-rank test p=0.009). holds promise impacting decision-making, patient stratification, treatment outcomes therapies.

Язык: Английский

Процитировано

3