Exploiting innate immunity for cancer immunotherapy

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

Published: Nov. 27, 2023

Abstract Immunotherapies have revolutionized the treatment paradigms of various types cancers. However, most these immunomodulatory strategies focus on harnessing adaptive immunity, mainly by inhibiting immunosuppressive signaling with immune checkpoint blockade, or enhancing immunostimulatory bispecific T cell engager and chimeric antigen receptor (CAR)-T cell. Although agents already achieved great success, only a tiny percentage patients could benefit from immunotherapies. Actually, immunotherapy efficacy is determined multiple components in tumor microenvironment beyond immunity. Cells innate arm system, such as macrophages, dendritic cells, myeloid-derived suppressor neutrophils, natural killer unconventional also participate cancer evasion surveillance. Considering that cornerstone antitumor response, utilizing immunity provides potential therapeutic options for control. Up to now, exploiting agonists stimulator interferon genes, CAR-macrophage -natural therapies, metabolic regulators, novel exhibited potent activities preclinical clinical studies. Here, we summarize latest insights into roles cells discuss advances arm-targeted strategies.

Language: Английский

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M1-like tumor-associated macrophages cascade a mesenchymal/stem-like phenotype of oral squamous cell carcinoma via the IL6/Stat3/THBS1 feedback loop

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Jan. 6, 2022

Abstract Background Tumor-associated macrophages (TAMs) have a leading position in the tumor microenvironment. Previously, we demonstrated that M1-like TAMs activated by exosome-transferred THBS1 promote malignant migration oral squamous cell carcinoma (OSCC). However, functional roles and associated molecular mechanisms of need to be further clarified OSCC. Methods Conditioned Media (CM) were harvested from exosome TAMs. We measured behaviors OSCC under treatment CM performing colony forming assays, invasion wound-healing spheroid assays vivo xenograft experiments. The underlying investigated RNA-seq, cytokines analysis, intracellular signaling pathway ChIP bioinformatics analysis validation. Results significantly promoted epithelial-mesenchymal transition (EMT) process, induced cancer-stem like cells (CSCs) upregulating expression MME MMP14 cells. Cytokine revealed shark increase IL6 secretion Blocking could weaken its effects on forming, invasion, migration, microsphere abilities Cellular indicated activation Jak/Stat3 treated Further RNA-seq an increased Bioinformatics prediction Stat3 directly transcription Conclusions proposed cascade mesenchymal/stem-like phenotype via IL6/Stat3/THBS1 feedback loop. A better understanding might facilitate development novel therapies for supplementing current strategies patients.

Language: Английский

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Extracellular vesicles in fatty liver promote a metastatic tumor microenvironment

Cell Metabolism, Journal Year: 2023, Volume and Issue: 35(7), P. 1209 - 1226.e13

Published: May 11, 2023

Language: Английский

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Reactive Oxygen Species Bridge the Gap between Chronic Inflammation and Tumor Development

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 22

Published: June 28, 2022

According to numerous animal studies, adverse environmental stimuli, including physical, chemical, and biological factors, can cause low-grade chronic inflammation subsequent tumor development. Human epidemiological evidence has confirmed the close relationship between tumorigenesis. However, mechanisms driving development of persistent toward tumorigenesis remain unclear. In this study, we assess potential role reactive oxygen species (ROS) associated in modulating inflammation-induced Recent reports have emphasized cross-talk oxidative stress many pathological processes. Exposure carcinogenic hazards may lead damage, which further stimulates infiltration various types inflammatory cells. turn, increased cytokine chemokine release from cells promotes ROS production lesions, even absence hazardous stimuli. Moreover, not only DNA damage but also participate cell proliferation, differentiation, apoptosis by several transcription factors signaling pathways. We summarize how changes redox state trigger lesions into tumors. Generally, cancer require an appropriate microenvironment support their growth, spread, metastasis, provide necessary catalyst for inflammation-driven cancer. conclusion, bridge gap development; therefore, targeting represents a new avenue prevention treatment

Language: Английский

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Pericytes in the tumor microenvironment

Cancer Letters, Journal Year: 2023, Volume and Issue: 556, P. 216074 - 216074

Published: Jan. 20, 2023

Pericytes are a type of mural cell located between the endothelial cells capillaries and basement membrane, which function to regulate capillary vasomotor maintain normal microcirculation local tissues organs have been identified as significant component in tumor microenvironment (TME). various interactions with different components TME, such constituting pre-metastatic niche, promoting growth cancer drug resistance through paracrine activity, inducing M2 macrophage polarization. While changes TME can affect number, phenotype, molecular markers pericytes. For example, pericyte detachment from facilitates situ invade circulating blood is beneficial membrane enzymatic hydrolysis proliferation budding, contribute angiogenesis metastasis. In this review, we discuss emerging role pericytes treatment related This review aimed provide more comprehensive understanding relationship tumors ideas for prevention malignant tumors.

Language: Английский

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Targeting myeloid-derived suppressor cells in tumor immunotherapy: Current, future and beyond

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

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Exosome-based delivery strategies for tumor therapy: an update on modification, loading, and clinical application

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

Published: Jan. 28, 2024

Malignancy is a major public health problem and among the leading lethal diseases worldwide. Although current tumor treatment methods have therapeutic effect to certain extent, they still some shortcomings such as poor water solubility, short half-life, local systemic toxicity. Therefore, how deliver agent so realize safe effective anti-tumor therapy become urgently be solved in this field. As medium of information exchange material transport between cells, exosomes are considered promising drug delivery carrier due their nano-size, good biocompatibility, natural targeting, easy modification. In review, we summarize recent advances isolation, identification, loading, modification carriers for alongside application therapy. Basic knowledge exosomes, biogenesis, sources, characterization methods, also introduced herein. addition, challenges related use vehicles discussed, along with future trends. This review provides scientific basis exosome systems oncological

Language: Английский

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The role of RNA methylation in tumor immunity and its potential in immunotherapy

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

Published: June 20, 2024

Abstract RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of methylation on tumor immunity. The primary types encompass N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), 3-methylcytidine (m3C). Compelling evidence underscores involvement regulating microenvironment (TME). By affecting translation stability through "writers", "erasers" "readers", influence dysregulation immune cells factors. Consequently, plays pivotal role immunity mediating various behaviors, encompassing proliferation, invasion, metastasis, etc. In this review, we discussed mechanisms several methylations, providing comprehensive overview their roles underlying within among immunocytes. exploring how these modifications mediate evasion, also examine potential applications immunotherapy. This review aims to provide novel insights strategies for identifying targets advancing cancer immunotherapy efficacy.

Language: Английский

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T-cell infiltration and its regulatory mechanisms in cancers: insights at single-cell resolution

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

Published: Feb. 2, 2024

Abstract Tumor-infiltrating T cells recognize, attack, and clear tumor cells, playing a central role in antitumor immune response. However, certain can impair this response help escape. Therefore, exploring the factors that influence T-cell infiltration is crucial to understand immunity improve therapeutic effect of cancer immunotherapy. The use single-cell RNA sequencing (scRNA-seq) allows high-resolution analysis precise composition with different phenotypes other microenvironmental factors, including non-immune stromal related molecules microenvironment various types. In review, we summarized research progress on crosstalk cytokines during using scRNA-seq provide insights into mechanisms regulating contribute new perspectives

Language: Английский

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Neutrophils in cancer: dual roles through intercellular interactions

Oncogene, Journal Year: 2024, Volume and Issue: unknown

Published: March 12, 2024

Language: Английский

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