Intercellular crosstalk between cancer cells and cancer-associated fibroblasts via exosomes in gastrointestinal tumors DOI Creative Commons

Longyang Cao,

Hong Ouyang

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

Published: Feb. 23, 2024

Gastrointestinal (GI) tumors are a significant global health threat, with high rates of morbidity and mortality. Exosomes contain various biologically active molecules like nucleic acids, proteins, lipids can serve as messengers for intercellular communication. They play critical roles in the exchange information between tumor cells microenvironment (TME). The TME consists mesenchymal components extracellular matrix (ECM), fibroblasts being most abundant cell type mesenchyme. Cancer-associated (CAFs) derived from normal stem that activated TME. CAFs secrete exosomes to modulate proliferation, invasion, migration, drug resistance, other biological processes tumors. Additionally, manipulate function behavior through direct cell-cell interactions. This review provides summary crosstalk GI exosomes, along potential underlying mechanisms.

Language: Английский

Potential anti-tumor effects of regulatory T cells in the tumor microenvironment: a review DOI Creative Commons
Yu Li, Cangang Zhang, Aimin Jiang

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 20, 2024

Abstract Regulatory T cells (Tregs) expressing the transcription factor FoxP3 are essential for maintaining immunological balance and a significant component of immunosuppressive tumor microenvironment (TME). Single-cell RNA sequencing (ScRNA-seq) technology has shown that Tregs exhibit plasticity functional diversity in various tumors within TME. This results playing dual role TME, which is not always centered around supporting progression as typically believed. Abundant data confirms anti-tumor activities their correlation with enhanced patient prognosis specific types malignancies. In this review, we summarize potential actions Tregs, including suppressing tumor-promoting inflammatory responses boosting immunity. addition, study outlines spatial temporal variations function to emphasize predictive significance malignancies may change. It comprehend effects improve therapy strategies.

Language: Английский

Citations

31
Cancer-associated fibroblasts: a versatile mediator in tumor progression, metastasis, and targeted therapy DOI Creative Commons

Tianchen Guo,

Junfen Xu

Cancer and Metastasis Reviews, Journal Year: 2024, Volume and Issue: 43(3), P. 1095 - 1116

Published: April 11, 2024

Abstract Tumor microenvironment (TME) has been demonstrated to play a significant role in tumor initiation, progression, and metastasis. Cancer-associated fibroblasts (CAFs) are the major component of TME exhibit heterogeneous properties their communication with cells. This heterogeneity CAFs can be attributed various origins, including quiescent fibroblasts, mesenchymal stem cells (MSCs), adipocytes, pericytes, endothelial cells, mesothelial Moreover, single-cell RNA sequencing identified diverse phenotypes CAFs, myofibroblastic (myCAFs) inflammatory (iCAFs) being most acknowledged, alongside newly discovered subtypes like antigen-presenting (apCAFs). Due these heterogeneities, exert multiple functions tumorigenesis, cancer stemness, angiogenesis, immunosuppression, metabolism, As result, targeted therapies aimed at TME, particularly focusing on rapidly developing, fueling promising future advanced tumor-targeted therapy.

Language: Английский

Citations

31
Dendritic Polymer‐Based Nanomedicines Remodel the Tumor Stroma: Improve Drug Penetration and Enhance Antitumor Immune Response DOI
Yuxin Zhang,

Zaixiang Fang,

Dayi Pan

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(25)

Published: March 12, 2024

Abstract The dense extracellular matrix (ECM) in solid tumors, contributed by cancer‐associated fibroblasts (CAFs), hinders penetration of drugs and diminishes their therapeutic outcomes. A sequential treatment strategy remodeling the ECM via a CAF modifier (dasatinib, DAS) is proposed to promote an immunogenic cell death (ICD) inducer (epirubicin, Epi) apoptotic vesicles, ultimately enhancing efficacy against breast cancer. Dendritic poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA)‐based nanomedicines (poly[OEGMA‐Dendron(G2)‐Gly‐Phe‐Leu‐Gly‐DAS] (P‐DAS) poly[OEGMA‐Dendron(G2)‐hydrazone‐Epi] (P‐Epi)) are developed for delivery DAS Epi, respectively. P‐DAS reprograms CAFs reduce collagen downregulating anabolism energy metabolism, thereby reducing deposition. regulated can enhance tumor P‐Epi strengthen its ICD effect, leading amplified antitumor immune response. In cancer‐bearing mice, this approach alleviates barrier, resulting reduced burden increased cytotoxic T lymphocyte infiltration, more encouragingly, synergizes effectively with anti‐programmed 1 (PD‐1) therapy, significantly inhibiting growth preventing lung metastasis. Furthermore, systemic toxicity barely detectable after P‐Epi. This opens new avenue treating desmoplastic tumors metabolically targeting overcome barrier.

Language: Английский

Citations

23
Understanding Cancer’s Defense against Topoisomerase-Active Drugs: A Comprehensive Review DOI Open Access
Nilesh Kumar Sharma, Anjali Bahot,

Gopinath Sekar

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(4), P. 680 - 680

Published: Feb. 6, 2024

In recent years, the emergence of cancer drug resistance has been one crucial tumor hallmarks that are supported by level genetic heterogeneity and complexities at cellular levels. Oxidative stress, immune evasion, metabolic reprogramming, overexpression ABC transporters, stemness among several key contributing molecular response mechanisms. Topo-active drugs, e.g., doxorubicin topotecan, clinically active utilized extensively against a wide variety human tumors often result in development failure to therapy. Thus, there is an urgent need for incremental comprehensive understanding mechanisms specifically context topo-active drugs. This review delves into intricate mechanistic aspects these intracellular extracellular explores use potential combinatorial approaches utilizing various drugs inhibitors pathways involved resistance. We believe this will help guide basic scientists, pre-clinicians, clinicians, policymakers toward holistic interdisciplinary strategies transcend resistance, renewing optimism ongoing battle cancer.

Language: Английский

Citations

17
Crosstalk between cancer-associated fibroblasts and regulated cell death in tumors: insights into apoptosis, autophagy, ferroptosis, and pyroptosis DOI Creative Commons
Cong Chen, Jian Liu,

Xia Lin

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: April 22, 2024

Abstract Cancer-associated fibroblasts (CAFs), the main stromal component of tumor microenvironment (TME), play multifaceted roles in cancer progression through paracrine signaling, exosome transfer, and cell interactions. Attractively, recent evidence indicates that CAFs can modulate various forms regulated death (RCD) adjacent cells, thus involving proliferation, therapy resistance, immune exclusion. Here, we present a brief introduction to basic knowledge RCD, including apoptosis, autophagy, ferroptosis, pyroptosis. In addition, further summarize different types RCD tumors are mediated by CAFs, as well effects these modes on CAFs. This review will deepen our understanding interactions between might offer novel therapeutic avenues for future treatments.

Language: Английский

Citations

17
Emerging role of immunogenic cell death in cancer immunotherapy: Advancing next-generation CAR-T cell immunotherapy by combination DOI
Zhaokai Zhou, Yumiao Mai, Ge Zhang

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 598, P. 217079 - 217079

Published: June 25, 2024

Language: Английский

Citations

17
Drug Delivery System Targeting Cancer-Associated Fibroblast for Improving Immunotherapy DOI Creative Commons

Zhongsong Zhang,

Rong Wang, Long Chen

et al.

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 483 - 503

Published: Jan. 1, 2025

Abstract: Cancer-associated fibroblasts (CAFs) are a heterogeneous population of non-malignant cells that play crucial role in the tumor microenvironment, increasingly recognized as key contributors to cancer progression, metastasis, and treatment resistance. So, targeting CAFs has always been considered an important part immunotherapy. However, improve efficacy therapy is currently major challenge. Nanomaterials show their unique advantages whole process. At present, nanomaterials have achieved significant accomplishments medical applications, particularly field cancer-targeted therapy, showing enormous potential. It confirmed can not only directly target CAFs, but also interact with microenvironment (TME) immune affect tumorigenesis. As for treatment, could enhance therapeutic effect many ways. Therefore, this review, we first summarized current understanding complex interactions between TME, cells, cells. Next, discussed common modern medicine respective impacts on tumors. Finally, focus application nano drug delivery system therapy. Keywords: cancer-associated fibroblasts, delivery, nanomedicine, immunotherapy

Language: Английский

Citations

3
Antigen-presenting cancer associated fibroblasts enhance antitumor immunity and predict immunotherapy response DOI Creative Commons
Junquan Song,

Rongyuan Wei,

Chenchen Liu

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 4, 2025

Cancer-associated fibroblasts (CAF) play a crucial role in tumor progression and immune regulation. However, the functional heterogeneity of CAFs remains unclear. Here, we identify antigen-presenting (apCAF), characterized by high MHC II expression, gastric cancer (GC) tumors find that apCAFs are preferentially located near tertiary lymphoid structures. Both vivo vitro experiments demonstrate promote T cell activation enhances its cytotoxic proliferative capacities, thereby strengthening cell-mediated anti-tumor immunity. Additionally, facilitate polarization macrophages toward pro-inflammatory phenotype. These polarized macrophages, turn, formation apCAFs, creating positive feedback loop amplifies responses. Notably, baseline immunotherapy responders across various types exhibit higher levels infiltration. This study advances understanding GC highlights as potential biomarker for predicting response pan-cancer.

Language: Английский

Citations

3
Nanomaterials in cancer immunotherapy: targeting cancer-associated fibroblasts DOI Creative Commons

Zhongsong Zhang,

Long Chen

Cancer Nanotechnology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 17, 2025

Emphasizing the significance of cancer-associated fibroblasts (CAFs), non-malignant yet pivotal players within tumor microenvironment (TME), this review illuminates role inflammatory subtype (iCAF) as catalysts in cancer proliferation, metastasis, and therapeutic resistance. Given their paramount importance, targeting CAFs emerges a robust strategy evolving landscape immunotherapy. Nanomaterials, distinguished by unique features malleability, hold considerable promise biomedicine, especially precision-oriented domain therapy. Their aptitude for modulating immune responses, amplifying drug efficacy through precise delivery, discerningly focusing on cells TME situates nanomaterials formidable tools to transcend boundaries set conventional treatments. This scrutinizes convoluted interplay among CAFs, cells, TME. It further showcases widely utilized management. We underscore potential nanoscale delivery systems directed at underscoring transformative power revolutionizing therapies, enhancing precision, culminating improved patient outcomes.

Language: Английский

Citations

2
Deciphering mechanical cues in the microenvironment: from non-malignant settings to tumor progression DOI Creative Commons
Yi‐Cheng Zhu,

Jiaoshun Chen,

Chen Chen

et al.

Biomarker Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 23, 2025

The tumor microenvironment functions as a dynamic and intricate ecosystem, comprising diverse array of cellular non-cellular components that precisely orchestrate pivotal behaviors, including invasion, metastasis, drug resistance. While unraveling the interplay between behaviors represents tremendous challenge, recent research illuminates crucial biological phenomenon known mechanotransduction. Within microenvironment, mechanical cues like tensile stress, shear stiffness play role by activating mechanosensitive effectors such PIEZO proteins, integrins, Yes-associated protein. This activation initiates cascades intrinsic signaling pathways, effectively linking physical properties tissues to their physiological pathophysiological processes morphogenesis, regeneration, immunity. mechanistic insight offers novel perspective on how within impact behaviors. intricacies are yet be fully elucidated, it exhibits distinct attributes from non-malignant tissues, elevated solid stresses, interstitial hypertension, augmented matrix stiffness, enhanced viscoelasticity. These traits exert notable influences progression treatment responses, enriching our comprehension multifaceted nature microenvironment. Through this innovative review, we aim provide new lens decipher contexts, broadening knowledge these factors promote or inhibit thus offering valuable insights identify potential targets for anti-tumor strategies.

Language: Английский

Citations

2