NK cells are never alone: crosstalk and communication in tumour microenvironments

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

Published: Feb. 16, 2023

Abstract Immune escape is a hallmark of cancer. The dynamic and heterogeneous tumour microenvironment (TME) causes insufficient infiltration poor efficacy natural killer (NK) cell-based immunotherapy, which becomes key factor triggering progression. Understanding the crosstalk between NK cells TME provides new insights for optimising immunotherapy. Here, we present advances in direct or indirect 9 specialised TMEs, including immune, metabolic, innervated niche, mechanical, microbial microenvironments, summarise TME-mediated mechanisms cell function inhibition, highlight potential targeted therapies NK-TME crosstalk. Importantly, discuss novel strategies to overcome inhibitory provide an attractive outlook future.

Language: Английский

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Cancer exosomes and natural killer cells dysfunction: biological roles, clinical significance and implications for immunotherapy

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

Published: Jan. 14, 2022

Abstract Tumor-derived exosomes (TDEs) play pivotal roles in several aspects of cancer biology. It is now evident that TDEs also favor tumor growth by negatively affecting anti-tumor immunity. As important sentinels immune surveillance system, natural killer (NK) cells can recognize malignant very early and counteract the development metastasis without a need for additional activation. Based on this rationale, adoptive transfer ex vivo expanded NK cells/NK cell lines, such as NK-92 cells, has attracted great attention widely studied promising immunotherapy treatment. However, exploiting various strategies, including secretion exosomes, are able to subvert responses. This paper reviews cancer-induced impairments with mechanistic insights. The clinical significance potential approaches nullify effects discussed.

Language: Английский

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Adoptive cellular immunotherapy for solid neoplasms beyond CAR-T

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

Published: Feb. 7, 2023

Abstract In recent decades, immune checkpoint blockade and chimeric antigen receptor T cell (CAR-T) therapy are two milestone achievements in clinical immunotherapy. However, both show limited efficacies most solid neoplasms, which necessitates the exploration of new immunotherapeutic modalities. The failure CAR-T several neoplasms is attributed to multiple factors, including low antigenicity tumor cells, infiltration effector diverse mechanisms immunosuppression microenvironment. New adoptive therapies have been attempted for TCR-T, CAR-natural killer cells (CAR-NK), CAR-macrophages (CAR-M). Compared CAR-T, these certain advantages treating neoplasms. this review, we summarized 40-year evolution therapies, then focused on advances CAR-NK, CAR-M discussed their potential applications.

Language: Английский

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Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 11, 2024

Abstract Diet, serving as a vital source of nutrients, exerts profound influence on human health and disease progression. Recently, dietary interventions have emerged promising adjunctive treatment strategies not only for cancer but also neurodegenerative diseases, autoimmune cardiovascular metabolic disorders. These demonstrated substantial potential in modulating metabolism, trajectory, therapeutic responses. Metabolic reprogramming is hallmark malignant progression, deeper understanding this phenomenon tumors its effects immune regulation significant challenge that impedes eradication. Dietary intake, key environmental factor, can tumor metabolism. Emerging evidence indicates might affect the nutrient availability tumors, thereby increasing efficacy treatments. However, intricate interplay between pathogenesis other diseases complex. Despite encouraging results, mechanisms underlying diet-based remain largely unexplored, often resulting underutilization management. In review, we aim to illuminate various interventions, including calorie restriction, fasting-mimicking diet, ketogenic protein restriction high-salt high-fat high-fiber aforementioned diseases. We explore multifaceted impacts these encompassing their immunomodulatory effects, biological impacts, molecular mechanisms. This review offers valuable insights into application therapies

Language: Английский

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m6A methylation: a process reshaping the tumour immune microenvironment and regulating immune evasion

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

Published: March 1, 2023

Abstract N6-methyladenosine (m 6 A) methylation is the most universal internal modification in eukaryotic mRNA. With elaborate functions executed by m A writers, erasers, and readers, modulation involved myriad physiological pathological processes. Extensive studies have demonstrated diverse tumours, with effects on tumorigenesis, metastasis, resistance. Recent evidence has revealed an emerging role of tumour immunoregulation, divergent patterns been microenvironment. To depict regulatory immune microenvironment (TIME) its effect evasion, this review focuses TIME, which characterized hypoxia, metabolic reprogramming, acidity, immunosuppression, outlines A-regulated TIME evasion under stimuli. Furthermore, anti-tumour cells are summarized.

Language: Английский

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Signaling pathways in brain tumors and therapeutic interventions

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

Published: Jan. 4, 2023

Abstract Brain tumors, although rare, contribute to distinct mortality and morbidity at all ages. Although there are few therapeutic options for brain enhanced biological understanding unexampled innovations in targeted therapies immunotherapies have considerably improved patients’ prognoses. Nonetheless, the reduced response rates unavoidable drug resistance of currently available treatment approaches become a barrier further improvement tumor (glioma, meningioma, CNS germ cell lymphoma) treatment. Previous literature data revealed that several different signaling pathways dysregulated tumor. Importantly, better targeting influences malignant behavior cells might open way development novel therapies. Thus, is an urgent need more comprehensive pathogenesis these which result greater progress approaches. This paper began with brief description epidemiology, incidence, risk factors, as well survival tumors. Next, major underlying tumors’ current therapies, including clinical trials, immunotherapies, system been systemically reviewed discussed. Finally, future perspective challenges strategies were emphasized.

Language: Английский

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Nanomedicine Remodels Tumor Microenvironment for Solid Tumor Immunotherapy

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(15), P. 10217 - 10233

Published: April 2, 2024

Although immunotherapy is relatively effective in treating hematological malignancies, their efficacy against solid tumors still suboptimal or even noneffective presently. Compared to cancers, exhibit strikingly different immunosuppressive microenvironment, severely deteriorating the of immunotherapy: (1) chemical features such as hypoxia and mild acidity suppress activity immune cells, (2) pro-tumorigenic domestication cells microenvironment within further undermines effectiveness immunotherapy, (3) dense physical barrier tumor tissues prevents intratumoral infiltration contact killing active cells. Therefore, we believe that reversing are critical priority for tumors. Due unique morphologies, structures, compositions, nanomedicines have become powerful tools achieving this goal. In Perspective, will first briefly introduce then summarize most recent progresses nanomedicine-based by remodeling immune-microenvironment a comprehensive manner. It highly expected Perspective aid advancing tumors, optimistic on future development burgeoning field.

Language: Английский

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Critical role of the gut microbiota in immune responses and cancer immunotherapy

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 14, 2024

The gut microbiota plays a critical role in the progression of human diseases, especially cancer. In recent decades, there has been accumulating evidence connections between and cancer immunotherapy. Therefore, understanding functional regulating immune responses to immunotherapy is crucial for developing precision medicine. this review, we extract insights from state-of-the-art research decipher complicated crosstalk among microbiota, systemic system, context Additionally, as can account immune-related adverse events, discuss potential interventions minimize these effects clinical application five microbiota-targeted strategies that precisely increase efficacy Finally, holds promising target immunotherapeutics, summarize current challenges provide general outlook on future directions field.

Language: Английский

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Mitochondrial quality control in human health and disease

Military Medical Research, Journal Year: 2024, Volume and Issue: 11(1)

Published: May 29, 2024

Abstract Mitochondria, the most crucial energy-generating organelles in eukaryotic cells, play a pivotal role regulating energy metabolism. However, their significance extends beyond this, as they are also indispensable vital life processes such cell proliferation, differentiation, immune responses, and redox balance. In response to various physiological signals or external stimuli, sophisticated mitochondrial quality control (MQC) mechanism has evolved, encompassing key like biogenesis, dynamics, mitophagy, which have garnered increasing attention from researchers unveil specific molecular mechanisms. this review, we present comprehensive summary of primary mechanisms functions regulators involved major components MQC. Furthermore, critical regulated by MQC its diverse roles progression systemic diseases been described detail. We discuss agonists antagonists targeting MQC, aiming explore potential therapeutic research prospects enhancing stabilize function.

Language: Английский

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Emerging role of gut microbiota in autoimmune diseases

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 3, 2024

Accumulating studies have indicated that the gut microbiota plays a pivotal role in onset of autoimmune diseases by engaging complex interactions with host. This review aims to provide comprehensive overview existing literatures concerning relationship between and diseases, shedding light on interplay microbiota, host immune system. Furthermore, we aim summarize impacts potential mechanisms underlie primarily focusing systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, type 1 diabetes mellitus, ulcerative colitis psoriasis. The present will emphasize clinical significance applications interventions based as innovative adjunctive therapies for diseases.

Language: Английский

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