Stromal architecture and fibroblast subpopulations with opposing effects on outcomes in hepatocellular carcinoma DOI Creative Commons
Yifei Cheng,

Xiaofang Chen,

Feng Li

и другие.

Cell Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Янв. 28, 2025

Abstract Dissecting the spatial heterogeneity of cancer-associated fibroblasts (CAFs) is vital for understanding tumor biology and therapeutic design. By combining pathological image analysis with proteomics, we revealed two stromal archetypes in hepatocellular carcinoma (HCC) different biological functions extracellular matrix compositions. Using paired single-cell RNA epigenomic sequencing Stereo-seq, fibroblast subsets CAF-FAP CAF-C7, whose enrichment strongly correlated opposing patient prognosis. We discovered functional units, one intratumor inflammatory hub featured by plus CD8_PDCD1 proximity other marginal wound-healing CAF-C7 Macrophage_SPP1 co-localization. Inhibiting combined anti-PD-1 orthotopic HCC models led to improved regression than either monotherapy. Collectively, our findings suggest stroma-targeted strategies based on defined archetypes, raising concept that CAFs change their transcriptional program intercellular crosstalk according context.

Язык: Английский

The cancer-immunity cycle: Indication, genotype, and immunotype DOI Creative Commons
Ira Mellman, Daniel S. Chen, Thomas Powles

и другие.

Immunity, Год журнала: 2023, Номер 56(10), С. 2188 - 2205

Опубликована: Окт. 1, 2023

The cancer-immunity cycle provides a framework to understand the series of events that generate anti-cancer immune responses. It emphasizes iterative nature response where killing tumor cells by T initiates subsequent rounds antigen presentation and cell stimulation, maintaining active immunity adapting it evolution. Any step can become rate-limiting, rendering system unable control growth. Here, we update based on remarkable progress past decade. Understanding mechanism checkpoint inhibition has evolved, as our view dendritic in sustaining anti-tumor immunity. We additionally account for role microenvironment facilitating, not just suppressing, response, discuss importance considering tumor's immunological phenotype, "immunotype". While these new insights add some complexity cycle, they also provide targets research therapeutic intervention.

Язык: Английский

Процитировано

389

Therapeutic developments in pancreatic cancer DOI
Zilun Hu, Eileen M. O’Reilly

Nature Reviews Gastroenterology & Hepatology, Год журнала: 2023, Номер 21(1), С. 7 - 24

Опубликована: Окт. 5, 2023

Язык: Английский

Процитировано

150

Cancer-associated fibroblast phenotypes are associated with patient outcome in non-small cell lung cancer DOI Creative Commons
Lena Cords, Stefanie Engler, Martina Haberecker

и другие.

Cancer Cell, Год журнала: 2024, Номер 42(3), С. 396 - 412.e5

Опубликована: Янв. 18, 2024

Despite advances in treatment, lung cancer survival rates remain low. A better understanding of the cellular heterogeneity and interplay cancer-associated fibroblasts (CAFs) within tumor microenvironment will support development personalized therapies. We report a spatially resolved single-cell imaging mass cytometry (IMC) analysis CAFs non-small cell cohort 1,070 patients. identify four prognostic patient groups based on 11 CAF phenotypes with distinct spatial distributions show that are independent factors for survival. The presence tumor-like is strongly correlated poor prognosis. In contrast, inflammatory interferon-response associated inflamed microenvironments higher High density matrix low immune infiltration negatively summary, our data phenotypic features outcome NSCLC.

Язык: Английский

Процитировано

101

Tumor initiation and early tumorigenesis: molecular mechanisms and interventional targets DOI Creative Commons
Shaosen Zhang,

Xinyi Xiao,

Yonglin Yi

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Июнь 18, 2024

Abstract Tumorigenesis is a multistep process, with oncogenic mutations in normal cell conferring clonal advantage as the initial event. However, despite pervasive somatic and expansion tissues, their transformation into cancer remains rare event, indicating presence of additional driver events for progression to an irreversible, highly heterogeneous, invasive lesion. Recently, researchers are emphasizing mechanisms environmental tumor risk factors epigenetic alterations that profoundly influencing early malignant evolution, independently inducing mutations. Additionally, evolution tumorigenesis reflects multifaceted interplay between cell-intrinsic identities various cell-extrinsic exert selective pressures either restrain uncontrolled proliferation or allow specific clones progress tumors. by which induce both intrinsic cellular competency remodel stress facilitate not fully understood. In this review, we summarize genetic, epigenetic, external events, effects on co-evolution transformed cells ecosystem during initiation evolution. A deeper understanding earliest molecular holds promise translational applications, predicting individuals at high-risk developing strategies intercept transformation.

Язык: Английский

Процитировано

68

The Interplay between Extracellular Matrix Remodeling and Cancer Therapeutics DOI Creative Commons
Jai Prakash, Yuval Shaked

Cancer Discovery, Год журнала: 2024, Номер 14(8), С. 1375 - 1388

Опубликована: Авг. 2, 2024

Abstract The extracellular matrix (ECM) is an abundant noncellular component of most solid tumors known to support tumor progression and metastasis. interplay between the ECM cancer therapeutics opens up new avenues in understanding biology. While protect from anticancer agents by serving as a biomechanical barrier, emerging studies show that various therapies induce remodeling, resulting therapy resistance progression. This review discusses critical issues this field including how influences treatment outcome, affect challenges associated with targeting ECM. Significance: intricate relationship reveals novel insights into biology its effective treatment. may anti-cancer agents, recent research highlights paradoxical role therapy-induced remodeling promoting explores key aspects therapeutics.

Язык: Английский

Процитировано

54

SHP2: A Pleiotropic Target at the Interface of Cancer and Its Microenvironment DOI Creative Commons
Nicole M. Sodir, Gaurav Pathria, Joanne I. Adamkewicz

и другие.

Cancer Discovery, Год журнала: 2023, Номер 13(11), С. 2339 - 2355

Опубликована: Сен. 8, 2023

Abstract The protein phosphatase SHP2/PTPN11 has been reported to be a key modulator of proliferative pathways in wide range malignancies. Intriguingly, SHP2 also described as critical regulator the tumor microenvironment. Based on this evidence is considered multifaceted target cancer, spurring notion that development direct inhibitors would provide twofold benefit intrinsic and extrinsic inhibition. In review, we will discuss role cancer microenvironment, clinical strategies which are leveraged combination agents improve therapeutic response. Significance: functions pleiotropic factor, its inhibition not only hinders growth but reshapes Although their single-agent activity may limited, hold potential being enhance depth durability response therapy.

Язык: Английский

Процитировано

45

Metformin-based nanomedicines for reprogramming tumor immune microenvironment DOI
Jieyu Liu, Xiaoling Li, Yinggang Li

и другие.

Theranostics, Год журнала: 2024, Номер 15(3), С. 993 - 1016

Опубликована: Дек. 2, 2024

Immunotherapy has transformed current cancer management, and it achieved significant progress over last decades. However, an immunosuppressive tumor microenvironment (TME) diminishes the effectiveness of immunotherapy by suppressing activity immune cells facilitating immune-evasion. Adenosine monophosphate-activated protein kinase (AMPK), a key modulator cellular energy metabolism homeostasis, gained growing attention in anti-tumor immunity. Metformin is usually considered as cornerstone diabetes its role activating AMPK pathway also been extensively explored therapy although findings on remain inconsistent. nanomedicine formulation found to hold potential reprogramming TME through immunometabolic modulation both cells. This review elaborates foundation via metformin-based nanomedicines, offering valuable insights for next generation therapy.

Язык: Английский

Процитировано

38

Mitochondria‐Targeted Nanoadjuvants Induced Multi‐Functional Immune‐Microenvironment Remodeling to Sensitize Tumor Radio‐Immunotherapy DOI Creative Commons
Zaigang Zhou, Cheng Li, Chao Li

и другие.

Advanced Science, Год журнала: 2024, Номер 11(26)

Опубликована: Май 5, 2024

Abstract It is newly revealed that collagen works as a physical barrier to tumor immune infiltration, oxygen perfusion, and depressor in solid tumors. Meanwhile, after radiotherapy (RT), the programmed death ligand‐1 (PD‐L1) overexpression transforming growth factor‐β (TGF‐β) excessive secretion would accelerate DNA damage repair trigger T cell exclusion limit RT efficacy. However, existing drugs or nanoparticles can hardly address these obstacles of highly effective simultaneously, effectively, easily. In this study, it inducing mitochondria dysfunction by using oxidative phosphorylation inhibitors like Lonidamine (LND) serve multi‐immune pathway regulation strategy through PD‐L1, collagen, TGF‐β co‐depression. Then, IR‐LND prepared combining mitochondria‐targeted molecule IR‐68 with LND, which then loaded liposomes (Lip) create IR‐LND@Lip nanoadjuvants. By doing this, more effectively sensitizes generating cold tumors into hot ones activation co‐inhibition. conclusion, combined treatment ultimately almost completely suppressed bladder breast

Язык: Английский

Процитировано

18

Cancer-associated fibroblast-derived extracellular vesicles: regulators and therapeutic targets in the tumor microenvironment DOI Open Access
Jindong Xie, Xinmei Lin, Xinpei Deng

и другие.

Cancer Drug Resistance, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Cancer-associated fibroblasts (CAFs) constitute a critical component of the tumor microenvironment (TME). CAFs can be reprogrammed by cancer cells, leading to production extracellular vesicles (EVs). These EVs serve as carriers for bioactive substances, including proteins, nucleic acids, and metabolic products, thereby facilitating progression. CAF-derived exert substantial influence on cell proliferation, invasion, metastasis, immunological environment, processes lymphangiogenesis angiogenesis. Despite their potential non-invasive biomarkers therapeutic delivery vehicles, clinical application is currently limited challenges in purification precise targeting. This review delineates diverse roles growth, immune evasion within TME.

Язык: Английский

Процитировано

6

Myeloid cell-derived apCAFs promote HNSCC progression by regulating proportion of CD4+ and CD8+ T cells DOI Creative Commons

Feilong Ren,

Lin Meng,

Shize Zheng

и другие.

Journal of Experimental & Clinical Cancer Research, Год журнала: 2025, Номер 44(1)

Опубликована: Янв. 31, 2025

Язык: Английский

Процитировано

3