Combining microenvironment normalization strategies to improve cancer immunotherapy DOI Creative Commons
Fotios Mpekris, Chrysovalantis Voutouri, James W. Baish

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(7), P. 3728 - 3737

Published: Feb. 3, 2020

Advances in immunotherapy have revolutionized the treatment of multiple cancers. Unfortunately, tumors usually impaired blood perfusion, which limits delivery therapeutics and cytotoxic immune cells to also results hypoxia-a hallmark abnormal tumor microenvironment (TME)-that causes immunosuppression. We proposed that normalization TME using antiangiogenic drugs and/or mechanotherapeutics can overcome these challenges. Recently, with checkpoint blockers was shown effectively induce vascular some types cancer. Although therapeutic approaches been used combination preclinical clinical studies, their combined effects on are not fully understood. To identify strategies for improved immunotherapy, we developed a mathematical framework incorporates complex interactions among various cancer cells, stroma, angiogenic molecules, vasculature. Model predictions were compared data from five previously reported experimental studies. found low doses improve when two treatments administered sequentially, but high less efficacious because excessive vessel pruning hypoxia. Stroma further increase efficacy benefit is additive normalization. conclude functionality dictates thus increased perfusion should be investigated as predictive biomarker response immunotherapy.

Language: Английский

The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth DOI Creative Commons
Karin E. de Visser, Johanna A. Joyce

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(3), P. 374 - 403

Published: March 1, 2023

Language: Английский

Citations

1595
Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives DOI Creative Commons

Xiaoqi Mao,

Jin Xu, Wei Wang

et al.

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Oct. 11, 2021

Abstract Cancer-associated fibroblasts (CAFs), a stromal cell population with cell-of-origin, phenotypic and functional heterogeneity, are the most essential components of tumor microenvironment (TME). Through multiple pathways, activated CAFs can promote growth, angiogenesis, invasion metastasis, along extracellular matrix (ECM) remodeling even chemoresistance. Numerous previous studies have confirmed critical role interaction between cells in tumorigenesis development. However, recently, mutual effects immune (TIME) been identified as another key factor promoting progression. The TIME mainly consists distinct populations islets is highly associated antitumor immunological state TME. interact tumor-infiltrating well other within via secretion various cytokines, growth factors, chemokines, exosomes effector molecules, consequently shaping an immunosuppressive TME that enables cancer to evade surveillance system. In-depth interactions, particularly complicated mechanisms connecting cells, might provide novel strategies for subsequent targeted immunotherapies. Herein, we shed light on recent advances regarding direct indirect crosstalk infiltrating further summarize possible immunoinhibitory induced by In addition, present current related CAF-targeting immunotherapies briefly describe some future perspectives CAF research end.

Language: Английский

Citations

1420
Exploring the NK cell platform for cancer immunotherapy DOI
Jacob A. Myers, Jeffrey S. Miller

Nature Reviews Clinical Oncology, Journal Year: 2020, Volume and Issue: 18(2), P. 85 - 100

Published: Sept. 15, 2020

Language: Английский

Citations

931
Cancer-associated fibroblasts: an emerging target of anti-cancer immunotherapy DOI Creative Commons
Tongyan Liu,

Chencheng Han,

Siwei Wang

et al.

Journal of Hematology & Oncology, Journal Year: 2019, Volume and Issue: 12(1)

Published: Aug. 28, 2019

Among all the stromal cells that present in tumor microenvironment, cancer-associated fibroblasts (CAFs) are one of most abundant and critical components mesenchyme, which not only provide physical support for but also play a key role promoting retarding tumorigenesis context-dependent manner. CAFs have been involved modulation many immune system, recent studies revealed their roles evasion poor responses to cancer immunotherapy. In this review, we describe our current understanding tumorigenic significance, origin, heterogeneity CAFs, as well different subtypes distinct cell types. More importantly, highlight potential therapeutic strategies target unleash system against tumor.

Language: Английский

Citations

709
TGFβ biology in cancer progression and immunotherapy DOI
Rik Derynck, Shannon J. Turley, Rosemary J. Akhurst

et al.

Nature Reviews Clinical Oncology, Journal Year: 2020, Volume and Issue: 18(1), P. 9 - 34

Published: July 24, 2020

Language: Английский

Citations

653
TGF-β in Hepatic Stellate Cell Activation and Liver Fibrogenesis—Updated 2019 DOI Creative Commons
Bedair Dewidar, Christoph Meyer, Steven Dooley

et al.

Cells, Journal Year: 2019, Volume and Issue: 8(11), P. 1419 - 1419

Published: Nov. 11, 2019

Liver fibrosis is an advanced liver disease condition, which could progress to cirrhosis and hepatocellular carcinoma. To date, there no direct approved antifibrotic therapy, current treatment mainly the removal of causative factor. Transforming growth factor (TGF)-β a master profibrogenic cytokine promising target treat fibrosis. However, TGF-β has broad biological functions its inhibition induces non-desirable side effects, override therapeutic benefits. Therefore, understanding pleiotropic effects upstream downstream regulatory mechanisms will help design better based therapeutics. Here, we summarize recent discoveries milestones on signaling pathway related hepatic stellate cell (HSC) activation, emphasizing research last five years. This comprises impact fibrogenesis processes, such as senescence, metabolism, reactive oxygen species generation, epigenetics, circadian rhythm, epithelial mesenchymal transition, endothelial-mesenchymal transition. We also describe influence microenvironment response HSC TGF-β. Finally, discuss new approaches pathway, name clinical trials, explain promises drawbacks that deserve be adequately addressed.

Language: Английский

Citations

599
Targeting TGF-β signal transduction for fibrosis and cancer therapy DOI Creative Commons
Dandan Peng,

Minyang Fu,

Manni Wang

et al.

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: April 23, 2022

Transforming growth factor β (TGF-β) has long been identified with its intensive involvement in early embryonic development and organogenesis, immune supervision, tissue repair, adult homeostasis. The role of TGF-β fibrosis cancer is complex sometimes even contradictory, exhibiting either inhibitory or promoting effects depending on the stage disease. Under pathological conditions, overexpressed causes epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition, cancer-associated fibroblast (CAF) formation, which leads to fibrotic disease, cancer. Given critical downstream molecules progression cancers, therapeutics targeting signaling appears be a promising strategy. However, due potential systemic cytotoxicity, lagged. In this review, we summarized biological process TGF-β, dual tumorigenesis, clinical application TGF-β-targeting therapies.

Language: Английский

Citations

584
Intratumoral heterogeneity in cancer progression and response to immunotherapy DOI
Ilio Vitale, Efrat Shema, Sherene Loi

et al.

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(2), P. 212 - 224

Published: Feb. 1, 2021

Language: Английский

Citations

578
The cytokine network involved in the host immune response to periodontitis DOI Creative Commons
Weiyi Pan, Qingxuan Wang, Qianming Chen

et al.

International Journal of Oral Science, Journal Year: 2019, Volume and Issue: 11(3)

Published: Sept. 1, 2019

Abstract Periodontitis is an inflammatory disease involving the destruction of both soft and hard tissue in periodontal region. Although dysbiosis local microbial community initiates inflammation, over-activation host immune response directly activates osteoclastic activity alveolar bone loss. Many studies have reported on cytokine network involved periodontitis its crucial pleiotropic effect recruitment specific immunocytes, control pathobionts induction or suppression activity. Nonetheless, particularities stimulation pathogens oral cavity that lead to complex are far from clarified. Thus, this review, we begin with up-to-date aetiological hypothesis summarize roles cytokines response. In addition, also latest cytokine-related therapeutic measures for disease.

Language: Английский

Citations

536
Targeting integrin pathways: mechanisms and advances in therapy DOI Creative Commons
Xiaocong Pang,

He Xu,

Zhiwei Qiu

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Jan. 2, 2023

Abstract Integrins are considered the main cell-adhesion transmembrane receptors that play multifaceted roles as extracellular matrix (ECM)-cytoskeletal linkers and transducers in biochemical mechanical signals between cells their environment a wide range of states health diseases. Integrin functions dependable on delicate balance active inactive status via multiple mechanisms, including protein-protein interactions, conformational changes, trafficking. Due to exposure cell surface sensitivity molecular blockade, integrins have been investigated pharmacological targets for nearly 40 years, but given complexity sometimes opposite characteristics, targeting integrin therapeutics has challenge. To date, only seven drugs successfully marketed, abciximab, eptifibatide, tirofiban, natalizumab, vedolizumab, lifitegrast, carotegrast. Currently, there approximately 90 kinds integrin-based therapeutic or imaging agents clinical studies, small molecules, antibodies, synthetic mimic peptides, antibody–drug conjugates (ADCs), chimeric antigen receptor (CAR) T-cell therapy, agents, etc. A serious lesson from past drug discovery research efforts is successes rely both deep understanding integrin-regulatory mechanisms unmet needs. Herein, we provide systematic complete review all family members integrin-mediated downstream signal transduction highlight ongoing develop new therapies/diagnoses bench clinic. In addition, further discuss trend development, how improve success rate trials therapies, key points research, basic translational research.

Language: Английский

Citations

487