Cancer-associated fibroblasts, tumor and radiotherapy: interactions in the tumor micro-environment DOI Creative Commons
Kris Raaijmakers, Gosse J. Adema, Johan Bussink

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: Dec. 19, 2024

Abstract Cancer-associated fibroblasts (CAFs) represent a group of genotypically non-malignant stromal cells in the tumor micro-environment (TME) solid tumors that encompasses up to 80% volume. Even though phenotypic diversity and plasticity CAFs complicates research, it is well-established can affect many aspects progression, including growth, invasion therapy resistance. Although anti-tumorigenic properties have been reported, majority research demonstrates pro-tumorigenic role for via (in)direct signaling cancer cells, immunomodulation extracellular matrix (ECM) remodeling. Following harsh therapeutic approaches such as radio- and/or chemotherapy, do not die but rather become senescent. Upon conversion towards senescence, characteristics are preserved or even amplified. Senescent continue promote cell resistance, modulate ECM, stimulate epithelial-to-mesenchymal transition (EMT) induce immunosuppression. Consequently, play significant survival, relapse potentially malignant transformation surviving following therapy. Modulating CAF functioning TME therefore critical area research. Proposed strategies enhance efficacy include reverting senescent quiescent phenotype selectively targeting (non-)senescent CAFs. In this review, we discuss before during therapy, with strong focus on radiotherapy. future, should be taken into account when designing treatment plans new approaches.

Language: Английский

Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer DOI Creative Commons
Moumita Kundu, Ramesh Butti, Venketesh K. Panda

et al.

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

Published: May 7, 2024

Abstract Breast cancer, the most frequent female malignancy, is often curable when detected at an early stage. The treatment of metastatic breast cancer more challenging and may be unresponsive to conventional therapy. Immunotherapy crucial for treating but its resistance a major limitation. tumor microenvironment (TME) vital in modulating immunotherapy response. Various microenvironmental components, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), are involved TME modulation cause resistance. This review highlights role stromal microenvironment, including involvement CAF-TAM interaction, alteration metabolism leading failure, other latest strategies, high throughput genomic screening, single-cell spatial omics techniques identifying immune genes regulating emphasizes therapeutic approach overcome through CAF reprogramming, TAM polarization, metabolism, alterations.

Language: Английский

Citations

44
Severely polarized extracellular acidity around tumour cells DOI
Qiang Feng, Zachary T. Bennett, Anthony Grichuk

et al.

Nature Biomedical Engineering, Journal Year: 2024, Volume and Issue: 8(6), P. 787 - 799

Published: March 4, 2024

Language: Английский

Citations

42
Tumour response to hypoxia: understanding the hypoxic tumour microenvironment to improve treatment outcome in solid tumours DOI Creative Commons
Kamilla J. A. Bigos, Conrado Guerrero Quiles, Sapna Lunj

et al.

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

Published: Jan. 30, 2024

Hypoxia is a common feature of solid tumours affecting their biology and response to therapy. One the main transcription factors activated by hypoxia hypoxia-inducible factor (HIF), which regulates expression genes involved in various aspects tumourigenesis including proliferative capacity, angiogenesis, immune evasion, metabolic reprogramming, extracellular matrix (ECM) remodelling, cell migration. This can negatively impact patient outcomes inducing therapeutic resistance. The importance clearly demonstrated continued research into finding clinically relevant biomarkers, hypoxia-targeting therapies. problems lack applicable methods detection, standardisation. Additionally, lot detecting do not take consideration complexity hypoxic tumour microenvironment (TME). Therefore, this needs further elucidation as approximately 50% are hypoxic. ECM important component TME, developed both cancer associated fibroblasts (CAFs) cells. However, it distinguish different roles develop biomarkers novel compounds. Fibronectin (FN), collagen (COL) hyaluronic acid (HA) components that create fibres. These fibres crosslinked specific enzymes lysyl oxidase (LOX) stiffness induces fibrosis. partially regulated HIFs. review highlights understanding role current data shows contradictory results on also indicates needed identifying CAF subtypes exact roles; with some showing pro-tumorigenic capacity others having anti-tumorigenic roles. has made difficult fully elucidate CAFs within TME. clear an area requires unravelling strategies target have resulted worsened prognosis. cells discussed been modulating environment. Which led development immunotherapies PD-L1. hypoxia-induced changes confer resistance conventional therapies, such chemotherapy, radiotherapy, immunotherapy. summarizes knowledge TME its implications for therapy It discusses potential prognostic predictive indictors treatment response, well challenges opportunities targeting clinical trials.

Language: Английский

Citations

27
Breaking Physical Barrier of Fibrotic Breast Cancer for Photodynamic Immunotherapy by Remodeling Tumor Extracellular Matrix and Reprogramming Cancer-Associated Fibroblasts DOI

Ziwen Qiu,

Yingtao Zhong, Zhen‐Ming Lu

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(13), P. 9713 - 9735

Published: March 20, 2024

Cancer-associated fibroblasts (CAFs) assist in breast cancer (BRCA) invasion and immune resistance by overproduction of extracellular matrix (ECM). Herein, we develop FPC@S, a photodynamic immunomodulator that targets the ECM, to improve immunotherapy for fibrotic BRCA. FPC@S combines tumor ECM-targeting peptide, photosensitizer (protoporphyrin IX) an antifibrotic drug (SIS3). After anchoring causes ECM remodeling BRCA cell death generating reactive oxygen species (ROS) situ. Interestingly, ROS-mediated can normalize blood vessel hypoxia turn facilitate more ROS production. Besides, upon acidic microenvironment, will release SIS3 reprograming CAFs reduce their activity but not kill them, thus inhibiting fibrosis while preventing metastasis. The natural physical barrier formed dense is consequently eliminated BRCA, allowing drugs cells penetrate deep into tumors have better efficacy. Furthermore, stimulate system effectively suppress primary, distant metastatic combining with checkpoint blockade therapy. This study provides different insights development targeted delivery systems exploration synergistic immunotherapeutic mechanisms against aggressive

Language: Английский

Citations

22
Dynamic interactions in the tumor niche: how the cross-talk between CAFs and the tumor microenvironment impacts resistance to therapy DOI Creative Commons
Oliwia Piwocka, Igor Piotrowski, Wiktoria Maria Suchorska

et al.

Frontiers in Molecular Biosciences, Journal Year: 2024, Volume and Issue: 11

Published: Feb. 22, 2024

The tumor microenvironment (TME) is a complex ecosystem of cells, signaling molecules, and extracellular matrix components that profoundly influence cancer progression. Among the key players in TME, cancer-associated fibroblasts (CAFs) have gained increasing attention for their diverse influential roles. CAFs are activated found abundantly within TME various types. contribute significantly to progression by promoting angiogenesis, remodeling matrix, modulating immune cell infiltration. In order microenvironment, engage cross-talk with other stromal through paracrine direct cell-cell interactions. This can result immunosuppression, proliferation, epithelial-mesenchymal transition, contributing disease Emerging evidence suggests play crucial role therapy resistance, including resistance chemotherapy radiotherapy. modulate response treatment secreting factors promote drug efflux, enhance DNA repair mechanisms, suppress apoptosis pathways. paper aims understand multifaceted functions discusses between sheds light on contibution resistance. Targeting or disrupting cells holds promise overcoming improving efficacy

Language: Английский

Citations

19
Targeting the PD-1/PD-L1 Signaling Pathway for Cancer Therapy: Focus on Biomarkers DOI Open Access
Αreti Strati, Christos Adamopoulos, Ioannis Kotsantis

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1235 - 1235

Published: Jan. 31, 2025

The PD1/PD-L1 axis plays an important immunosuppressive role during the T-cell-mediated immune response, which is essential for physiological homeostasis of system. biology immunological microenvironment extremely complex and crucial development treatment strategies immunotherapy. Characterization immunological, genomic or transcriptomic landscape cancer patients could allow discrimination between responders non-responders to anti-PD-1/PD-L1 therapy. Immune checkpoint inhibitor (ICI) therapy has shown remarkable efficacy in a variety malignancies landmark trials fundamentally changed Current research focuses on maximize patient selection therapy, clarify mechanisms resistance, improve existing biomarkers, including PD-L1 expression tumor mutational burden (TMB), discover new biomarkers. In this review, we focus function PD-1/PD-L1 signaling pathway discuss genomic, epigenetic receiving Finally, provide overview clinical testing antibodies against PD-1/PD-L1.

Language: Английский

Citations

2
Targeting fibroblast activation protein (FAP): advances in CAR-T cell, antibody, and vaccine in cancer immunotherapy DOI

Sedigheh Shahvali,

Niloufar Rahiman, Mahmoud Reza Jaafari

et al.

Drug Delivery and Translational Research, Journal Year: 2023, Volume and Issue: 13(7), P. 2041 - 2056

Published: Feb. 25, 2023

Language: Английский

Citations

36
Fibroblasts as Turned Agents in Cancer Progression DOI Open Access
Robert Wieder

Cancers, Journal Year: 2023, Volume and Issue: 15(7), P. 2014 - 2014

Published: March 28, 2023

Differentiated epithelial cells reside in the homeostatic microenvironment of native organ stroma. The stroma supports their normal function, G

Language: Английский

Citations

27
Immunotherapy resistance in solid tumors: mechanisms and potential solutions DOI Creative Commons
Daniel S. Lefler, Steven Manobianco, Babar Bashir

et al.

Cancer Biology & Therapy, Journal Year: 2024, Volume and Issue: 25(1)

Published: Feb. 22, 2024

While the emergence of immunotherapies has fundamentally altered management solid tumors, cancers exploit many complex biological mechanisms that result in resistance to these agents. These encompass a broad range cellular activities - from modification traditional paradigms immunity via antigen presentation and immunoregulation metabolic modifications manipulation tumor microenvironment. Intervening on intricate processes may provide clinical benefit patients with tumors by overcoming immunotherapies, which is why it become an area tremendous research interest practice-changing implications. This review details major ways avoid both natural through primary (innate) secondary (acquired) resistance, considers available emerging therapeutic approaches immunotherapy resistance.

Language: Английский

Citations

15
The tumor microenvironment: shaping cancer progression and treatment response DOI
Sharav Desai, Vipul P. Patel, Kunal Bhosle

et al.

Journal of Chemotherapy, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 30

Published: Jan. 5, 2024

The tumor microenvironment (TME) plays a crucial role in cancer progression and treatment response. It comprises complex network of stromal cells, immune extracellular matrix, blood vessels, all which interact with cells influence behaviour. This review article provides an in-depth examination the TME, focusing on signaling molecules, ECM, along commonly available therapeutic compounds that target these components. Moreover, we explore TME as novel strategy for discovering new anti-tumor drugs. dynamic adaptive nature offers opportunities targeting specific cellular interactions pathways. We discuss emerging approaches, such combination therapies simultaneously modulate TME. Finally, address challenges future prospects Overcoming drug resistance, improving delivery, identifying targets within are among discussed. also highlight potential personalized medicine integration technologies, immunotherapy nanotechnology, TME-targeted therapies. comprehensive insights into its implications. Understanding TME's complexity components offer promising avenues development improved patient outcomes.

Language: Английский

Citations

13