Targeting Cancer‐Associated Fibroblasts: Eliminate or Reprogram? DOI Creative Commons
Masaya Yamazaki, Takatsugu Ishimoto

Cancer Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

ABSTRACT Cancer‐associated fibroblasts (CAFs) are key components of the tumor microenvironment (TME). Given their various roles in progression and treatment resistance, CAFs promising therapeutic targets cancer. The elimination tumor‐promoting has been investigated animal models to determine whether it effectively suppresses growth. Based on recent evidence, several simple strategies have proposed eliminate attenuate these features. In addition, attention focused critical role that play immunosuppressive TME. Therefore, functional reprogramming combination with immune checkpoint inhibitors also as a possible approach. However, although potential widely characterized, plasticity heterogeneity complicate understanding properties present difficulties for clinical application. Moreover, identification tumor‐suppressive highlights necessity development approaches can distinguish switch between an appropriate manner. this review, we introduce origins diversity CAFs, cancer, current aimed at targeting including ongoing evaluations.

Language: Английский

Molecular mechanisms of tumor resistance to radiotherapy DOI Creative Commons
Yu Wu, Yingqiu Song, Runze Wang

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: June 15, 2023

Abstract Background Cancer is the most prevalent cause of death globally, and radiotherapy considered standard care for solid tumors, including lung, breast, esophageal, colorectal cancers glioblastoma. Resistance to radiation can lead local treatment failure even cancer recurrence. Main body In this review, we have extensively discussed several crucial aspects that resistance therapy, radiation-induced DNA damage repair, cell cycle arrest, apoptosis escape, abundance stem cells, modification cells their microenvironment, presence exosomal non-coding RNA, metabolic reprogramming, ferroptosis. We aim focus on molecular mechanisms in relation these discuss possible targets improve outcomes. Conclusions Studying responsible its interactions with tumor environment will help responses radiotherapy. Our review provides a foundation identify overcome obstacles effective

Language: Английский

Citations

194
Inflammation: the incubator of the tumor microenvironment DOI
Dominic Denk, Florian R. Greten

Trends in cancer, Journal Year: 2022, Volume and Issue: 8(11), P. 901 - 914

Published: July 28, 2022

Language: Английский

Citations

153
Combining ferroptosis induction with MDSC blockade renders primary tumours and metastases in liver sensitive to immune checkpoint blockade DOI Creative Commons
Claire Conche, Fabian Finkelmeier, Marina Pešić

et al.

Gut, Journal Year: 2023, Volume and Issue: 72(9), P. 1774 - 1782

Published: Jan. 27, 2023

Investigating the effect of ferroptosis in tumour microenvironment to identify combinatory therapy for liver cancer treatment.Glutathione peroxidase 4 (GPx4), which is considered master regulator ferroptosis, was genetically altered murine models hepatocellular carcinoma (HCC) and colorectal (CRC) analyse on cells immune microenvironment. The findings served as foundation identification additional targets combine with ferroptotic inducer treatment HCC metastasis.Surprisingly, hepatocyte-restricted GPx4 loss does not suppress tumourigenesis. Instead, GPx4-associated hepatocyte death causes a suppressive response characterised by CXCL10-dependent infiltration cytotoxic CD8+ T that counterbalanced PD-L1 upregulation well marked HMGB1-mediated myeloid derived suppressor cell (MDSC) infiltration. Blocking PD-1 or HMGB1 unleashes activation prolongs survival mice Gpx4-deficient tumours. A triple combination inducing natural compound withaferin A, CXCR2 inhibitor SB225002 α-PD-1 greatly improves wild-type In contrast, same affect growth subcutaneously grown CRC organoids, while it decreases their metastatic liver.Our data highlight context-specific ferroptosis-induced could be therapeutically exploited primary tumours metastases.

Language: Английский

Citations

151
Cancer cell plasticity during tumor progression, metastasis and response to therapy DOI
Andrea Pérez-González, Kevin Bévant, Cédric Blanpain

et al.

Nature Cancer, Journal Year: 2023, Volume and Issue: 4(8), P. 1063 - 1082

Published: Aug. 3, 2023

Language: Английский

Citations

143
Cancer-Associated Fibroblasts in Inflammation and Antitumor Immunity DOI Creative Commons
Kilian B. Kennel, Müge Bozlar, Adalbert F. De Valk

et al.

Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 29(6), P. 1009 - 1016

Published: Nov. 18, 2022

Abstract Tumor-associated inflammation (TAI) is a feature of essentially all cancers and can confer both tumor-promoting -suppressive functions. Cancer-associated fibroblasts (CAF) comprise one very heterogeneous cellular component the tumor microenvironment characterized by high degree plasticity. Recent single-cell sequencing analyses revealed distinct CAF populations in various human helped to define key subtypes, such as myofibroblastic, inflammatory, antigen-presenting CAFs, with first two being present virtually tumors. Importantly, these three are involved modulate positive negative consequences TAI. The remarkable plasticity CAFs allows them shift phenotypically functionally response environmental changes. In this review, we describe how nurture suppress adaptive immunity. We also summarize recently emerging evidence pertaining tumor-suppressive functions context Finally, therapeutic concepts that aim at modulating or depleting immunosuppressive synergize immunotherapy.

Language: Английский

Citations

130
Cellular senescence and the tumour microenvironment DOI Creative Commons
Masaki Takasugi, Yuya Yoshida, Naoko Ohtani

et al.

Molecular Oncology, Journal Year: 2022, Volume and Issue: 16(18), P. 3333 - 3351

Published: June 8, 2022

The senescence-associated secretory phenotype (SASP), where senescent cells produce a variety of secreted proteins including inflammatory cytokines, chemokines, matrix remodelling factors, growth factors and so on, plays pivotal but varying roles in the tumour microenvironment. effects SASP on surrounding microenvironment depend cell type process cellular senescence induction, which is often associated with innate immunity. Via SASP-mediated paracrine effects, can remodel tissues by modulating character adjacent cells, such as stromal, immune well cancer cells. both tumour-suppressive tumour-promoting observed surveillance (tumour-suppressive) suppression anti-tumour immunity most cancer-associated fibroblasts T (tumour-promoting). In this review, we discuss features emphasis their context-dependency that determines whether they promote or suppress development. Potential usage recently developed drugs (senomorphics) selectively kill (senolytics) therapy are also discussed.

Language: Английский

Citations

95
The advent of immune stimulating CAFs in cancer DOI
Maria Tsoumakidou

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(4), P. 258 - 269

Published: Feb. 17, 2023

Language: Английский

Citations

76
Single‐Nucleus RNA Sequencing and Spatial Transcriptomics Reveal the Immunological Microenvironment of Cervical Squamous Cell Carcinoma DOI Creative Commons
Zhihua Ou, Shitong Lin, Jiaying Qiu

et al.

Advanced Science, Journal Year: 2022, Volume and Issue: 9(29)

Published: Aug. 19, 2022

The effective treatment of advanced cervical cancer remains challenging. Herein, single-nucleus RNA sequencing (snRNA-seq) and SpaTial enhanced resolution omics-sequencing (Stereo-seq) are used to investigate the immunological microenvironment squamous cell carcinoma (CSCC). expression levels most immune suppressive genes in tumor inflammation areas CSCC not significantly higher than those non-cancer samples, except for LGALS9 IDO1. Stronger signals CD56

Language: Английский

Citations

74
Expansion of T memory stem cells with superior anti-tumor immunity by Urolithin A-induced mitophagy DOI Creative Commons
Dominic Denk,

Valentina Petrocelli,

Claire Conche

et al.

Immunity, Journal Year: 2022, Volume and Issue: 55(11), P. 2059 - 2073.e8

Published: Oct. 19, 2022

T memory stem cells (TSCM) display increased self-renewal and prolonged survival capabilities, thus preventing cell exhaustion promoting effective anti-tumor responses. TSCM can be expanded by Urolithin A (UA), which is produced the commensal gut microbiome from foods rich in ellagitannins known to improve mitochondrial health. Oral UA administration tumor-bearing mice conferred strong CD8+ immunity, whereas ex vivo pre-treated displayed improved function upon adoptive transfer. UA-induced formation depended on Pink1-mediated mitophagy triggering cytosolic release of phosphatase Pgam5. Cytosolic Pgam5 dephosphorylated β-catenin, drove Wnt signaling compensatory biogenesis. Collectively, we unravel a critical pathway linking suggest that well-tolerated metabolic compound represents an attractive option immune therapy.

Language: Английский

Citations

72
Hypoxia Potentiates the Inflammatory Fibroblast Phenotype Promoted by Pancreatic Cancer Cell–Derived Cytokines DOI

Simon Schwörer,

Francesco V. Cimino, Manon Ros

et al.

Cancer Research, Journal Year: 2023, Volume and Issue: 83(10), P. 1596 - 1610

Published: March 13, 2023

Abstract Cancer-associated fibroblasts (CAF) are a major cell type in the stroma of solid tumors and can exert both tumor-promoting tumor-restraining functions. CAF heterogeneity is frequently observed pancreatic ductal adenocarcinoma (PDAC), tumor characterized by dense hypoxic that features myofibroblastic CAFs (myCAF) inflammatory (iCAF) thought to have opposing roles progression. While be driven part cell–produced cytokines, other determinants shaping identity function largely unknown. In vivo, we found iCAFs displayed gene expression biochemical profile were enriched regions PDAC tumors, while myCAFs excluded from these regions. Hypoxia led acquire an signature synergized with cancer cell–derived cytokines promote iCAF phenotype HIF1α-dependent fashion. Furthermore, HIF1α stabilization was sufficient induce stromal cells introduced into organoid cocultures growth. These findings indicate hypoxia-induced as regulator promoter progression PDAC. Significance: microenvironment potentiates cytokine-induced promotes See related commentary Fuentes Taniguchi, p. 1560

Language: Английский

Citations

62