The regulatory roles of RNA-binding proteins in the tumour immune microenvironment of gastrointestinal malignancies DOI Creative Commons
Dongqi Li, Xiangyu Chu, Weikang Liu

и другие.

RNA Biology, Год журнала: 2024, Номер 22(1), С. 1 - 14

Опубликована: Дек. 24, 2024

The crosstalk between the tumour immune microenvironment (TIME) and cells promote evasion resistance to immunotherapy in gastrointestinal (GI) tumours. Post-transcriptional regulation of genes is pivotal GI tumours progression, RNA-binding proteins (RBPs) serve as key regulators via their domains. RBPs may exhibit either anti-tumour or pro-tumour functions by influencing TIME through modulation mRNAs non-coding RNAs expression, well post-transcriptional modifications, primarily N6-methyladenosine (m6A). Aberrant RBPs, such HuR YBX1, typically enhances escape impacts prognosis patients. Further, while targeting offers a promising strategy for improving cancers, mechanisms which regulate these remain poorly understood, therapeutic application still its early stages. This review summarizes current advances exploring roles regulating expression effect on tumours, then providing theoretical insights RBP-targeted cancer therapies.

Язык: Английский

Nanocatalysts for modulating antitumor immunity: fabrication, mechanisms and applications DOI
Xianbo Wu, Yuqing Li, Mei Wen

и другие.

Chemical Society Reviews, Год журнала: 2024, Номер 53(5), С. 2643 - 2692

Опубликована: Янв. 1, 2024

This review discusses the structures and engineering strategies of nanocatalysts, highlighting their underlying mechanisms applications in cancer immunotherapy.

Язык: Английский

Процитировано

33
Metabolic engineering for optimized CAR-T cell therapy DOI

Sarah McPhedran,

Gillian Carleton, Julian J. Lum

и другие.

Nature Metabolism, Год журнала: 2024, Номер 6(3), С. 396 - 408

Опубликована: Фев. 22, 2024

Язык: Английский

Процитировано

14
Targeting the kynurenine pathway: another therapeutic opportunity in the metabolic crosstalk between cancer and immune cells DOI Creative Commons
Irene Kang, George Theodoropoulos, Medhi Wangpaichitr

и другие.

Frontiers in Oncology, Год журнала: 2025, Номер 14

Опубликована: Янв. 22, 2025

The pivotal role of metabolic reprogramming in cancer-related drug resistance, through the tryptophan-catabolized kynurenine pathway (KP), has been particularly underscored recent research. This pathway, driven by indoleamine 2,3-dioxygenase 1 (IDO1), facilitates immune evasion and promotes tumor progression fostering an immunosuppressive environment. In Phase III investigation combination IDO1 inhibition with checkpoint inhibitors (ICIs), therapy was not efficacious. this review, we revisit current advances, explore future directions, emphasize importance dual KP rate-limiting enzymes tryptophan 2,3-dioxygenase-2 (TDO2) appropriate patient populations. We propose that may maximize therapeutic potential inhibition. Additionally, delve into complex cellular interactions cancer dependencies within microenvironment (TME). Insights from preclinical studies, clinical trials, promising combinations will be discussed to elucidate promote a clear path forward for direction research outcomes.

Язык: Английский

Процитировано

1
Exploring Neutrophil Heterogeneity and Plasticity in Health and Disease DOI Creative Commons
Conny Gysemans,

Mateson Beya,

E.A. Pedace

и другие.

Biomedicines, Год журнала: 2025, Номер 13(3), С. 597 - 597

Опубликована: Март 1, 2025

Neutrophils, the most abundant polymorphonuclear leukocytes, are critical first responders to infection, and have historically been underappreciated in terms of their functional complexity within immune response. Once viewed primarily as short-lived, innate cells with limited plasticity, recent research has illuminated considerable heterogeneity diverse roles, which extend beyond involvement steady-state immunity. This review seeks provide an updated analysis neutrophil development, maturation, heterogeneity, a focus on how these characteristics influence modulation both healthy diseased tissues. Beginning origin neutrophils, we explore maturation into effector evolving roles defense under homeostatic disease-associated conditions. We then delve discussing breakthroughs that challenge traditional view neutrophils uniform population. address significant advances made identifying distinct subsets, emerging complexities challenges remain fully understanding diversity. Finally, highlight future directions opportunities for continued exploration this rapidly advancing field, shedding light insights could open new avenues therapeutic interventions.

Язык: Английский

Процитировано

1
The Role of the Kynurenine/AhR Pathway in Diseases Related to Metabolism and Cancer DOI Open Access
Amir Shadboorestan,

Meriem Koual,

Julien Dairou

и другие.

International Journal of Tryptophan Research, Год журнала: 2023, Номер 16

Опубликована: Янв. 1, 2023

The Aryl hydrocarbon receptor (AhR) is a xenobiotic and endobiotic receptor, which regulates many cellular processes from contaminant metabolism to immunomodulation. Consequently, it also involved in pathophysiological pathways now represents potential therapeutical target. In this review, we will highlight the ancestral function of protein together with an illustration its ligand’s battery, emphasizing different responses triggered by these high diverse molecules. Among them, several members kynurenine pathway (one key process tryptophan catabolism) are AhR agonists subsequently regulatory functions. We finally display interplay between Tryptophan (Trp) catabolism dysregulation metabolic drawing hypothesis on involvement cancer-related processes.

Язык: Английский

Процитировано

17
Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer DOI Creative Commons
Nadia Boufaied, Paolo Chetta, Tarek Hallal

и другие.

Cancer Research, Год журнала: 2024, Номер 84(11), С. 1834 - 1855

Опубликована: Июнь 4, 2024

Abstract Cancer cells exhibit metabolic plasticity to meet oncogene-driven dependencies while coping with nutrient availability. A better understanding of how systemic metabolism impacts the accumulation metabolites that reprogram tumor microenvironment (TME) and drive cancer could facilitate development precision nutrition approaches. Using Hi-MYC prostate mouse model, we demonstrated an obesogenic high-fat diet (HFD) rich in saturated fats accelerates c-MYC–driven invasive through rewiring. Although c-MYC modulated key pathways, interaction HFD was necessary induce glycolysis lactate tumors. These changes were associated augmented infiltration CD206+ PD-L1+ tumor-associated macrophages (TAM) FOXP3+ regulatory T cells, as well activation transcriptional programs linked disease progression therapy resistance. Lactate itself also stimulated neoangiogenesis cell migration, which significantly reduced following treatment dehydrogenase inhibitor FX11. In patients cancer, high fat intake increased body mass index glycolytic features promote M2-like TAMs. Finally, upregulation dehydrogenase, indicative a lactagenic phenotype, shorter time biochemical recurrence independent clinical cohorts. This work identifies cooperation between genetic drivers hijack TME oncometabolite accumulation. sets stage for assessment prognostic biomarker supports strategies dietary intervention direct lactagenesis blockade treating advanced cancer. Significance: driven by MYC reprograms promotes progression, supporting potential therapeutic target See related commentary Frigo, p. 1742

Язык: Английский

Процитировано

7
Oleuropein-driven reprogramming of the myeloid cell compartment to sensitise tumours to PD-1/PD-L1 blockade strategies DOI Creative Commons
Ester Blanco, Noelia Silva-Pilipich, Ana Bocanegra

и другие.

British Journal of Cancer, Год журнала: 2024, Номер 130(5), С. 869 - 879

Опубликована: Янв. 9, 2024

Abstract Background Previous studies have shown that functional systemic immunity is required for the efficacy of PD-1/PD-L1 blockade immunotherapies in cancer. Hence, reprogramming immunosuppressive dysfunctional myeloid cells could overcome resistance to cancer immunotherapy. Methods Reprogramming tumour-associated with oleuropein was studied by quantitative differential proteomics, phenotypic and assays mice lung patients. Combinations two different delivery methods anti-PD-1 antibodies were tested colorectal tumour models immunotherapy-resistant models. Results Oleuropein treatment reprogrammed monocytic granulocytic myeloid-derived suppressor cells, macrophages towards differentiation immunostimulatory subsets. regulated major programmes associated immune modulation which potentiated T cell responses PD-1 blockade. delivered strategies, either systemically or expressed within tumours using a self-amplifying RNA vector. Combination therapies increased infiltration dendritic draining lymph nodes, leading antitumour responses. Potent therapeutic activities achieved colon resistant immunotherapies, even complete regression. Discussion significantly improves outcome immunotherapy strategies cells.

Язык: Английский

Процитировано

6
Discovering the strength of immunometabolism in cancer therapy: Employing metabolic pathways to enhance immune responses DOI

Huldani Huldani,

Jitendra Malviya, Paul Rodrigues

и другие.

Cell Biochemistry and Function, Год журнала: 2024, Номер 42(2)

Опубликована: Янв. 28, 2024

Abstract Immunometabolism, which studies cellular metabolism and immune cell function, is a possible cancer treatment. Metabolic pathways regulate activation, differentiation, effector functions, crucial to tumor identification elimination. Immune evasion growth can result from microenvironment metabolic dysregulation. These boost antitumor immunity. This overview discusses metabolism, including glycolysis, oxidative phosphorylation, amino acid, lipid metabolism. Amino acid manipulations may improve activity Combination therapy using immunometabolism‐based strategies enhance therapeutic efficacy. The complexity of the network, biomarker development, challenges, future approaches are all covered, along with summary case demonstrating effectiveness therapy. Metabolomics, stable isotope tracing, single‐cell analysis, computational modeling also reviewed for immunometabolism research. Personalized combination treatments considered. review adds expertise sheds light on treatments' ability treatment immunological response. Also, in this review, we discussed response altering increase against malignancies.

Язык: Английский

Процитировано

6
Metabolic landscape of head and neck squamous cell carcinoma informs a novel kynurenine/Siglec‐15 axis in immune escape DOI Creative Commons

X Zhang,

Jianbo Shi, Shufang Jin

и другие.

Cancer Communications, Год журнала: 2024, Номер 44(6), С. 670 - 694

Опубликована: Май 12, 2024

Abstract Background Metabolic reprograming and immune escape are two hallmarks of cancer. However, how metabolic disorders drive in head neck squamous cell carcinoma (HNSCC) remains unclear. Therefore, the aim present study was to investigate landscape HNSCC its mechanism driving escape. Methods Analysis paired tumor tissues adjacent normal from 69 patients performed using liquid/gas chromatography‐mass spectrometry RNA‐sequencing. The tumor‐promoting function kynurenine (Kyn) explored vitro vivo. downstream target Kyn investigated CD8 + T cells. regulation cells after Siglec‐15 overexpression An engineering nanoparticle established deliver small interfering RNA (siS15), association with immunotherapy response were investigated. between programmed death 1 (PD‐1) analyzed a patient cohort. Results A total 178 metabolites showed significant dysregulation HNSCC, including carbohydrates, lipids lipid‐like molecules, amino acids. Among these, acid metabolism most significantly altered, especially Kyn, which promoted proliferation metastasis. In addition, checkpoint molecules upregulated Kyn‐high based on Furthermore, tumor‐derived transferred into induced functional exhaustion, blocking transporters restored killing activity. Accroding results, mechanistically, transcriptionally regulated expression via aryl hydrocarbon receptor (AhR), by suppressing infiltration activation. Targeting AhR vivo reduced Kyn‐mediated intratumoral capacity. Finally, NH 2 ‐modified mesoporous silica designed siS15, status enhanced anti‐PD‐1 efficacy tumor‐bearing immunocompetent mice. Clinically, positively correlated PD‐1 tissues. Conclusions findings describe comprehensively reveal that Kyn/Siglec‐15 axis may be novel potential immunometabolism mechanism, providing promising therapeutic strategy for cancers.

Язык: Английский

Процитировано

6
Neuroscience in peripheral cancers: tumors hijacking nerves and neuroimmune crosstalk DOI Creative Commons

Hua‐yang Fan,

Xin‐hua Liang, Ya‐ling Tang

и другие.

MedComm, Год журнала: 2024, Номер 5(11)

Опубликована: Окт. 31, 2024

Abstract Cancer neuroscience is an emerging field that investigates the intricate relationship between nervous system and cancer, gaining increasing recognition for its importance. The central governs development of directly affects brain tumors, peripheral (PNS) shapes tumor microenvironment (TME) tumors. Both systems are crucial in cancer initiation progression, with recent studies revealing a more role PNS within TME. Tumors not only invade nerves but also persuade them through remodeling to further promote malignancy, creating bidirectional interaction cancers. Notably, immune cells contribute this communication, forming triangular influences protumor inflammation effectiveness immunotherapy. This review delves into mechanisms connecting focusing on how various cell types influence nerve‒tumor interactions, emphasizing clinical relevance nerve‒immune dynamics. By deepening our understanding interplay nerves, cells, has potential reshape biology insights, inspire innovative therapies, improve outcomes patients.

Язык: Английский

Процитировано

6