Immune evasion in esophageal squamous cell cancer: From the perspective of tumor microenvironment DOI Creative Commons
Rongyang Li,

Bing Huang,

Hui Tian

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 12

Published: Jan. 9, 2023

Esophageal cancer (EC) is one of the most life-threatening malignancies worldwide. squamous cell carcinoma (ESCC) dominant subtype, accounting for approximately 90% new incident EC each year. Although multidisciplinary treatment strategies have advanced rapidly, patients with ESCC are often diagnosed at stage and long-term prognosis remains unsatisfactory. In recent decades, immunotherapy, such as immune checkpoint inhibitors (ICIs), tumor vaccines, chimeric antigen receptor T-cell (CAR-T) therapy, has been successfully used in clinical practice a novel therapy treating tumors, bringing hope to patients. However, only small fraction achieved benefits due primary or acquired resistance. Immune evasion plays pivotal role initiation progression ESCC. Therefore, thorough understanding mechanisms by which cells escape from anti-tumor immunity necessary more effective strategy. It widely recognized that closely associated crosstalk between microenvironment (TME). TME dynamic complex comprehensive system including not cellular components but also non-cellular components, influence hallmarks fates outside. Novel immunotherapy targeting tumor-favorable represents promising strategy achieve better therapeutic responses this review, we provide an overview ESCC, mainly focusing on molecular underlie addition, discuss challenges opportunities precision TME.

Language: Английский

The role of IL-6/JAK2/STAT3 signaling pathway in cancers DOI Creative Commons
Bei Huang,

Xiaoling Lang,

Xihong Li

et al.

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Dec. 16, 2022

Interleukin-6 (IL-6) is a pleiotropic cytokine involved in immune regulation. It can activate janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway. As one the important signal transduction pathways cells, JAK2/STAT3 pathway plays critical role cell proliferation differentiation by affecting activation state downstream effector molecules. The tumorigenesis development. contributes to formation tumor inflammatory microenvironment closely related occurrence development many human tumors. This article focuses on relationship between IL-6/JAK2/STAT3 liver cancer, breast colorectal gastric lung pancreatic cancer ovarian hoping provide references for research treatment targeting key molecules

Language: Английский

Citations

208
Dual Effect of Immune Cells within Tumour Microenvironment: Pro- and Anti-Tumour Effects and Their Triggers DOI Open Access

Alicia Cristina Peña-Romero,

Esteban Orenes‐Piñero

Cancers, Journal Year: 2022, Volume and Issue: 14(7), P. 1681 - 1681

Published: March 25, 2022

Our body is constantly exposed to pathogens or external threats, but with the immune response that our can develop, we fight off and defeat possible attacks infections. Nevertheless, sometimes this threat comes from an internal factor. Situations such as existence of a tumour also cause system (IS) be put on alert. Indeed, link between immunology cancer evident these days, IS being used one important targets for treating cancer. able eliminate those abnormal damaged cells found in body, preventing uncontrolled proliferation lead However, several cases, escape IS. It has been observed cells, extracellular matrix, blood vessels, fat various molecules could support growth development. Thus, developing receives structural support, irrigation energy, among other resources, making its survival progression possible. All components accompany help survive grow are called microenvironment (TME). Given importance presence development process, review will focus TME: cells. Immune anti-tumour protecting us against cells; nevertheless, they behave pro-tumoural thus promoting survival. In review, pro-tumour immunity discussed. addition, TME influence dual effect analysed.

Language: Английский

Citations

149
Tumor promoting roles of IL-10, TGF-β, IL-4, and IL-35: Its implications in cancer immunotherapy DOI Creative Commons
Bhalchandra Mirlekar

SAGE Open Medicine, Journal Year: 2022, Volume and Issue: 10

Published: Jan. 1, 2022

Cytokines play a critical role in regulating host immune response toward cancer and determining the overall fate of tumorigenesis. The tumor microenvironment is dominated mainly by immune-suppressive cytokines that control effector antitumor immunity promote survival proliferation cells, which ultimately leads to enhanced growth. In addition heterogeneous cells present within milieu are significant source cytokines. These classified into broad range; however, most types, interleukin-10, transforming growth factor-β, interleukin-4, interleukin-35 consistently reported as help metastasis. emerging concern treatment hijacking restraining activity niche due highly environment. This review summarizes precise functions modulating contexture its implication developing effective immune-therapeutic approaches.Recent effort geared novel approaches faces challenges sustained mutations milieu. crucial an environment dictates critically covers aspects predominant such dictating tumorigenesis how targeting these can development better drug regimens for cancer.

Language: Английский

Citations

130
Targeted nanomedicines remodeling immunosuppressive tumor microenvironment for enhanced cancer immunotherapy DOI Creative Commons

Yanyan Xu,

Jingyuan Xiong, Xiyang Sun

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 12(12), P. 4327 - 4347

Published: Nov. 4, 2022

Cancer immunotherapy has significantly flourished and revolutionized the limited conventional tumor therapies, on account of its good safety long-term memory ability. Discouragingly, low patient response rates potential immune-related side effects make it rather challenging to literally bring from bench bedside. However, become evident that, although immunosuppressive microenvironment (TME) plays a pivotal role in facilitating progression metastasis, also provides various targets for remodeling TME, which can consequently bolster effectiveness antitumor suppression. Additionally, particular characteristics turn, be exploited as avenues designing diverse precise targeting nanomedicines. In general, is urgent necessity deliver nanomedicines thus improving therapeutic outcomes clinical translation prospects immunotherapy. Herein, we will illustrate several formation mechanisms TME. More importantly, variety strategies concerning TME strengthening patients' immune systems, reviewed. Ultimately, discuss existing obstacles future perspectives development Hopefully, thriving bloom vibrancy further exploration comprehensive cancer treatment.

Language: Английский

Citations

125
ABC transporters affects tumor immune microenvironment to regulate cancer immunotherapy and multidrug resistance DOI Creative Commons
Jingyi Fan, Kenneth K.W. To, Zhe‐Sheng Chen

et al.

Drug Resistance Updates, Journal Year: 2022, Volume and Issue: 66, P. 100905 - 100905

Published: Nov. 30, 2022

Multidrug resistance (MDR) is the phenomenon in which cancer cells simultaneously develop to a broad spectrum of structurally and mechanistically unrelated drugs. MDR severely hinders effective treatment major cause chemotherapy failure. ATP-binding cassette (ABC) transporters are extensively expressed various body tissues, actively transport endogenous exogenous substrates through biological membranes. Overexpression ABC frequently observed cells, promotes efflux chemotherapeutic drugs reduces their intracellular accumulation. Increasing evidence suggests that regulate tumor immune microenvironment (TIME) by transporting cytokines, thus controlling anti-tumor immunity sensitivity anticancer On other hand, expression regulated cytokines signaling molecules. Targeted inhibition transporter or function can enhance efficacy checkpoint inhibitors promoting microenvironment. This review provides an update on recent research progress this field.

Language: Английский

Citations

98
YY1 complex in M2 macrophage promotes prostate cancer progression by upregulating IL-6 DOI Creative Commons
Saisai Chen, Kai Lǚ,

Yue Hou

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2023, Volume and Issue: 11(4), P. e006020 - e006020

Published: April 1, 2023

Background Tumor-associated macrophages are mainly polarized into the M2 phenotype, remodeling tumor microenvironment and promoting progression by secreting various cytokines. Methods Tissue microarray consisting of prostate cancer (PCa), normal prostate, lymph node metastatic samples from patients with PCa were stained Yin Yang 1 (YY1) CD163. Transgenic mice overexpressing YY1 constructed to observe tumorigenesis. Furthermore, in vivo vitro experiments, including CRISPR-Cas9 knock-out, RNA sequencing, chromatin immunoprecipitation (ChIP) liquid–liquid phase separation (LLPS) assays, performed investigate role mechanism microenvironment. Results was highly expressed associated poorer clinical outcomes. The proportion tumor-infiltrated increased transgenic YY1. In contrast, proliferation activity anti-tumoral T lymphocytes suppressed. Treatment targeting on using an M2-targeting peptide-modified liposome carrier suppressed cell lung metastasis generated synergistic effects PD-1 blockade. IL-4/STAT6 pathway regulated YY1, macrophage-induced upregulating IL-6. conducting H3K27ac-ChIP-seq THP-1, we found that thousands enhancers gained during macrophage polarization, these M2-specific enriched ChIP-seq signals. addition, IL-6 enhancer upregulated expression through long-range interaction promoter macrophages. During formed LLPS, which p300, p65, CEBPB acted as transcriptional cofactors. Conclusions Phase complex enhancer–promoter interactions, thereby increasing progression.

Language: Английский

Citations

53
A metal ions-mediated natural small molecules carrier-free injectable hydrogel achieving laser-mediated photo-Fenton-like anticancer therapy by synergy apoptosis/cuproptosis/anti-inflammation DOI Creative Commons

Wenmin Pi,

Linying Wu,

Jihui Lu

et al.

Bioactive Materials, Journal Year: 2023, Volume and Issue: 29, P. 98 - 115

Published: July 5, 2023

Tumor microenvironment (TME) plays an important role in the tumorigenesis, proliferation, invasion and metastasis. Thereby developing synergistic anticancer strategies with multiple mechanisms are urgent. Copper is widely used treatment of tumor chemodynamic therapy (CDT) due to its excellent laser-mediated photo-Fenton-like reaction. Additionally, copper can induce cell death through cuproptosis, which a new modality different from known has great promise treatment. Herein, we report natural small molecules carrier-free injectable hydrogel (NCTD Gel) consisted Cu2+-mediated self-assembled glycyrrhizic acid (GA) norcantharidin (NCTD), mainly governed by coordination hydrogen bonds. Under 808 nm laser irradiation, NCTD Gel produce reactive oxygen species (ROS), consume glutathione (GSH) overcome hypoxia TME, leading synergistically regulate TME via apoptosis, cuproptosis anti-inflammation. In addition, Gel's CDT display high selectivity good biocompatibility as it relies on weak acidity H2O2 overexpression TME. Notably, components originated clinical agents preparation process easy, green economical, without any excipients. This study provides antitumor strategy, prospect industrial production transformation.

Language: Английский

Citations

53
Chronic inflammation and cancer; the two sides of a coin DOI
Queenie Fernandes,

Varghese Inchakalody,

Takwa Bedhiafi

et al.

Life Sciences, Journal Year: 2023, Volume and Issue: 338, P. 122390 - 122390

Published: Dec. 30, 2023

Language: Английский

Citations

46
Unraveling the tumor microenvironment: Insights into cancer metastasis and therapeutic strategies DOI Creative Commons
Mohamed El‐Tanani, Syed Arman Rabbani, Rasha Babiker

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 591, P. 216894 - 216894

Published: April 16, 2024

This comprehensive review delves into the pivotal role of tumor microenvironment (TME) in cancer metastasis and therapeutic response, offering fresh insights intricate interplay between cells their surrounding milieu. The TME, a dynamic ecosystem comprising diverse cellular acellular elements, not only fosters progression but also profoundly affects efficacy conventional emerging therapies. Through nuanced exploration, this illuminates multifaceted nature elucidating its capacity to engender drug resistance via mechanisms such as hypoxia, immune evasion, establishment physical barriers delivery. Moreover, it investigates innovative approaches aimed at targeting including stromal reprogramming, modulation, extracellular matrix (ECM)-targeting agents, personalized medicine strategies, highlighting potential augment treatment outcomes. Furthermore, critically evaluates challenges posed by complexity heterogeneity which contribute variable responses potentially unintended consequences. underscores need identify robust biomarkers advance predictive models anticipate outcomes, well advocate for combination therapies that address multiple facets TME. Finally, emphasizes necessity an interdisciplinary approach integration cutting-edge technologies unravel intricacies thereby facilitating development more effective, adaptable, treatments. By providing critical current state TME research implications future oncology, highlights evolving landscape field.

Language: Английский

Citations

46
Targeting myeloid-derived suppressor cells in tumor immunotherapy: Current, future and beyond DOI Creative Commons
Yang Zhao, Junfeng Du, Xiaofei Shen

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 17, 2023

Myeloid-derived suppressor cells (MDSCs) are one of the major negative regulators in tumor microenvironment (TME) due to their potent immunosuppressive capacity. MDSCs products myeloid progenitor abnormal differentiation bone marrow, which inhibits immune response mediated by T cells, natural killer and dendritic cells; promotes generation regulatory tumor-associated macrophages; drives escape; finally leads progression metastasis. In this review, we highlight key features biology TME that being explored as potential targets for immunotherapy. We discuss therapies approaches aim reprogram from immunostimulatory circumstance, prevents MDSC immunosuppression activity; differentiation; impacts recruitment abundance site. also summarize current advances identification rational combinatorial strategies improve clinical efficacy outcomes cancer patients, via deeply understanding pursuing mechanisms characterization suppression TME.

Language: Английский

Citations

43