Exploring the crosstalk between endothelial cells, immune cells, and immune checkpoints in the tumor microenvironment: new insights and therapeutic implications

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(9)

Published: Sept. 4, 2023

Abstract The tumor microenvironment (TME) is a highly intricate milieu, comprising multitude of components, including immune cells and stromal cells, that exert profound influence on initiation progression. Within the TME, angiogenesis predominantly orchestrated by endothelial (ECs), which foster proliferation metastasis malignant cells. interplay between with ECs complex can either bolster or hinder system. Thus, comprehensive understanding crosstalk essential to advance development immunotherapeutic interventions. Despite recent progress, underlying molecular mechanisms govern remain elusive. Nevertheless, immunomodulatory function has emerged as pivotal determinant response. In light this, study relationship checkpoints garnered considerable attention in field immunotherapy. By targeting specific pathways signaling molecules associated novel strategies may be devised enhance efficacy current treatments. this vein, we sought elucidate ECs, ultimate goal identifying therapeutic targets charting new avenues for

Language: Английский

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Significance of Melatonin in the Regulation of Circadian Rhythms and Disease Management

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(8), P. 5541 - 5571

Published: Jan. 11, 2024

Language: Английский

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Circadian regulation of cancer stem cells and the tumor microenvironment during metastasis

Nature Cancer, Journal Year: 2024, Volume and Issue: 5(4), P. 546 - 556

Published: April 23, 2024

Language: Английский

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Tumor-associated macrophage-specific CD155 contributes to M2-phenotype transition, immunosuppression, and tumor progression in colorectal cancer

Journal for ImmunoTherapy of Cancer, Journal Year: 2022, Volume and Issue: 10(9), P. e004219 - e004219

Published: Sept. 1, 2022

Background Onco-immunogenic molecule CD155 is overexpressed in various tumor microenvironments (TME) including colorectal cancer (CRC). Tumor-associated macrophages (TAMs) are the most abundant immune cells CRC TME and play a vital role progression metastasis. Most studies have focused on investigating of cell-specific progression, while contribution TAMs-specific still unknown. Here, we sought to investigate expression pattern TAMs its immunity progression. Methods patterns paratumor or adjacent normal tissue were analyzed 50 patients with using flow cytometry 141 immunohistochemistry. The correlation level M1 M2 phenotypic transition was analyzed. macrophage-specific response investigated vitro vivo. We further effect regulation macrophages. Results from clinical samples showed robustly higher than tissues. at III/IV stages compared I/II negatively associated survival CRC. + an phenotype interleukin (IL)-10 transforming growth factor (TGF)-β. promoted cell migration, invasion, supporting findings analysis. This mainly regulated by TGF-β-induced STAT3 activation-mediated release matrix metalloproteinases (MMP)2 MMP9 cells. –⁄– bone marrow transplantation wild-type mice, as well CD155– treatment, antitumor mice ectopic model. Additionally, released IL-4 trigger indicating regulatory development TAMs. Conclusions These indicated that responsible for M2-phenotype transition, immunosuppression, specific localization could turn into potential therapeutic target treatment.

Language: Английский

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Melatonin: A mitochondrial resident with a diverse skill set

Life Sciences, Journal Year: 2022, Volume and Issue: 301, P. 120612 - 120612

Published: May 4, 2022

Language: Английский

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Non-coding RNAs and macrophage interaction in tumor progression

Critical Reviews in Oncology/Hematology, Journal Year: 2022, Volume and Issue: 173, P. 103680 - 103680

Published: April 8, 2022

Language: Английский

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Tumor-associated Macrophages (TAMs) in Cancer Resistance; Modulation by Natural Products

Current Topics in Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 23(12), P. 1104 - 1122

Published: Feb. 1, 2023

Abstract: Tumor-associated macrophages (TAMs) play a pivotal role in the progression and re-sistance of tumors to different anticancer drugs. TAMs can modulate tumor microenvironment (TME) favor immune system exhaustion. The interactions with TME affect function cytotoxic CD8+ T lymphocytes (CTLs) natural killer (NK) cells. Furthermore, induce cancer cell proliferation by releasing some growth factors, such as transforming factor (TGF)-β. have several positive cross-talks other suppressive cells regulatory (Tregs), myeloid-derived suppressor (MDSCs), cancer-associated fibroblasts (CAFs), cells, leading release prolif-eration growth. These also invasion migration angiogenesis, metastasis. inhibition is an intriguing strategy for overcoming resistance suppression Some natural-derived agents melatonin, curcumin, resveratrol, apigenin, flavonoids shown ability TME, including TAMs. adjuvants may be able boost antitumor immunity through modulation This review explains modulatory effects well-known naturally derived on activity these useful suppressing invasion.

Language: Английский

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Extracellular vesicles remodel tumor environment for cancer immunotherapy

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

Published: Dec. 13, 2023

Tumor immunotherapy has transformed neoplastic disease management, yet low response rates and immune complications persist as major challenges. Extracellular vesicles including exosomes have emerged therapeutic agents actively involved in a diverse range of pathological conditions. Mounting evidence suggests that alterations the quantity composition extracellular (EVs) contribute to remodeling immune-suppressive tumor microenvironment (TME), thereby influencing efficacy immunotherapy. This revelation sparked clinical interest utilizing EVs for sensitization. In this perspective article, we present comprehensive overview origins, generation, interplay among various components within TME. Furthermore, discuss pivotal role reshaping TME during tumorigenesis their specific cargo, such PD-1 non-coding RNA, which influence phenotypes critical cells Additionally, summarize applications different anti-tumor therapies, latest advancements engineering cancer immunotherapy, challenges encountered translation. light these findings, advocate broader understanding impact on TME, will unveil overlooked vulnerabilities potentially enhance existing immunotherapies.

Language: Английский

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Immunoregulation by resveratrol; implications for normal tissue protection and tumour suppression

Clinical and Experimental Pharmacology and Physiology, Journal Year: 2023, Volume and Issue: 50(5), P. 353 - 368

Published: Feb. 14, 2023

Immune reactions are involved in both tumour and normal tissue response to therapy. Elevated secretion of certain chemokines, exosomes cytokines triggers inflammation, pain, fibrosis ulceration among other side effects. On the hand, tumour-promoting molecules suppresses activity anticancer immune cells facilitates proliferation malignant cells. Novel drugs such as checkpoint inhibitors (ICIs) boost immunity via inducing natural killer (NK) CD8+ T lymphocytes. Certain chemotherapy radiotherapy may induce tumour, however, have severe effects for tissues through stimulation several responses. Thus, administration products with low be a promising approach modulate system organs. Resveratrol is well-known phenol diverse on tumours. To date, large number experiments confirmed potential resveratrol an adjuvant. This review focuses ensuing or suppression responses after drugs. Later on, immunoregulatory following exposure agents will discussed.

Language: Английский

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Targeting oral tumor microenvironment for effective therapy

Cancer Cell International, Journal Year: 2023, Volume and Issue: 23(1)

Published: May 23, 2023

Oral cancers are among the common head and neck malignancies. Different anticancer therapy modalities such as chemotherapy, immunotherapy, radiation therapy, also targeted molecular may be prescribed for targeting oral Traditionally, it has been assumed that malignant cells alone by chemotherapy radiotherapy suppresses tumor growth. In last decade, a large number of experiments have confirmed pivotal role other secreted molecules in microenvironment (TME) on progression. Extracellular matrix immunosuppressive tumor-associated macrophages, myeloid-derived suppressor (MDSCs), cancer-associated fibroblasts (CAFs), regulatory T (Tregs) play key roles progression tumors like resistance to therapy. On hand, infiltrated CD4 + CD8 lymphocytes, natural killer (NK) anti-tumor suppress proliferation cells. Modulation extracellular cells, stimulation immunity suggested treat malignancies more effectively. Furthermore, administration some adjuvants or combination this review, we discuss various interactions between cancer TME. review basic mechanisms within TME cause Potential targets approaches overcoming will reviewed. The findings potential therapeutic clinical studies

Language: Английский

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