IL-18 and VEGF-A trigger type 2 innate lymphoid cell accumulation and pro-tumoral function in chronic myeloid leukemia DOI Creative Commons
Benedetta Fiordi, Valentina Salvestrini,

Gabriele Gugliotta

et al.

Haematologica, Journal Year: 2023, Volume and Issue: unknown

Published: April 6, 2023

Chronic myeloid leukemia (CML) is a hematologic malignancy associated to an unregulated growth of cells in bone marrow (BM) and peripheral blood (PB), characterized by the BCR-ABL1 translocation. Given known cytokine impairment leukemic niche CML, we investigated impact this microenvironmental dysregulation on innate lymphoid (ILC), whose role cancer has recently emerged. Three ILC subsets are identified based transcriptional profiles secretion. We observed that interleukin 18 (IL-18) vascular endothelial factor A (VEGF-A) increased CML patients' sera ILC2 enriched PB BM. found IL-18 drives proliferation highly express CXCR4 CXCR7 BM-homing receptors, potentially explaining their enrichment BM, respectively. Next, showed hyper-activated through tumor-derived VEGF-Adependent mechanism, which leads higher IL-13 In response IL-13, increase clonogenic capacity. Finally, discovered pro-tumoral axis involving VEGF-A, was disrupted upon tyrosine kinase inhibitor treatment, normalizing levels all these players patients responding therapy. Overall, our study uncovers involvement progression, mediated VEGF-A IL-18.

Language: Английский

A CD38-directed, single-chain T-cell engager targets leukemia stem cells through IFN-γ–induced CD38 expression DOI
Mariam Murtadha, Miso Park,

Yinghui Zhu

et al.

Blood, Journal Year: 2024, Volume and Issue: 143(16), P. 1599 - 1615

Published: Feb. 23, 2024

Language: Английский

Citations

6
The STAT family: Key transcription factors mediating crosstalk between cancer stem cells and tumor immune microenvironment DOI

Mengxuan Zhu,

Suyao Li,

Xin Cao

et al.

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 88, P. 18 - 31

Published: Nov. 19, 2022

Language: Английский

Citations

22
Microbiota in cancer: molecular mechanisms and therapeutic interventions DOI Creative Commons
Zhou Chen, Defeng Guan,

Zhengfeng Wang

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(6)

Published: Nov. 5, 2023

Abstract The diverse bacterial populations within the symbiotic microbiota play a pivotal role in both health and disease. Microbiota modulates critical aspects of tumor biology including cell proliferation, invasion, metastasis. This regulation occurs through mechanisms like enhancing genomic damage, hindering gene repair, activating aberrant signaling pathways, influencing metabolism, promoting revascularization, remodeling immune microenvironment. These microbiota‐mediated effects significantly impact overall survival recurrence tumors after surgery by affecting efficacy chemoradiotherapy. Moreover, leveraging for development biovectors, probiotics, prebiotics, synbiotics, addition to utilizing antibiotics, dietary adjustments, defensins, oncolytic virotherapy, fecal transplantation, offers promising alternatives cancer treatment. Nonetheless, due extensive nature microbiota, along with heterogeneity, molecular underlying remain subject intense debate. In this context, we refocus on various cancers, delving into pathways associated its derivatives, reshaping microenvironmental matrix, tolerance treatments such as chemotherapy radiotherapy. exploration aims shed light novel perspectives potential applications field.

Language: Английский

Citations

13
The unique role of innate lymphoid cells in cancer and the hepatic microenvironment DOI Creative Commons
Sophie Curio, Gabrielle T. Belz

Cellular and Molecular Immunology, Journal Year: 2022, Volume and Issue: 19(9), P. 1012 - 1029

Published: Aug. 12, 2022

Cancer is a complex disease, and despite incredible progress over the last decade, it remains leading cause of death worldwide. Liver cancers, including hepatocellular carcinoma (HCC), liver metastases are distinct from other cancers in that they typically emerge as consequence long-term low-grade inflammation. Understanding mechanisms underpin inflammation-driven tissue remodeling hepatic immune environment likely to provide new insights into much needed treatments for this devastating disease. Group 1 innate lymphoid cells (ILCs), which include natural killer (NK) ILC1s, particularly enriched thought contribute pathogenesis number diseases, cancer. NK an attractive, but underexplored, therapeutic target disease due their role immunosurveillance ability recognize eliminate malignant cells. ILC1s closely related share many phenotypic features with less well studied. Thus, utility immunotherapeutic approaches not yet understood. Here, we review our current understanding ILCs cancer particular focus on liver-related diseases.

Language: Английский

Citations

18
FOXO1 orchestrates the intestinal homeostasis via neuronal signaling in group 3 innate lymphoid cells DOI Creative Commons
Fei Shao, Zhen Liu, Qinglin Wei

et al.

The Journal of Experimental Medicine, Journal Year: 2023, Volume and Issue: 220(10)

Published: July 21, 2023

The neuro-immune regulation is associated with homeostasis of the intestine. Intestinal group 3 innate lymphoid cells (ILC3s) are tissue-resident lymphocytes whose functions affected by intestine niche. However, how a gut neuronal signal coordinates immune response ILC3s largely unknown. Here, we found that cyclic adenosine monophosphate (cAMP) signaling exacerbated inflammatory and attenuated expression level transcription factor forkhead box O1 (FOXO1) in ILC3s. Deficiency FOXO1 drove hyperactivation resulted inflammation independently T cells. Mechanistically, promoted neuropeptide receptor VIPR2 inhibited adrenoceptor ADRA2A FOXO1-related balanced activation under steady condition or during colitis. Moreover, chronic stress elevated cAMP downregulated level, exacerbating intestinal inflammation. Our findings reveal balances via VIP adrenergic regulates homeostasis.

Language: Английский

Citations

10
NKp46 enhances type 1 innate lymphoid cell proliferation and function and anti-acute myeloid leukemia activity DOI Creative Commons
Rui Ma, Zhenlong Li,

Hejun Tang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 24, 2025

NKp46 is a critical regulator of natural killer (NK) cell immunity, but its function in non-NK innate immune cells remains unclear. Here, we show that indispensable for expressing IL-2 receptor-α (IL-2Rα) by liver-resident type-1 lymphoid (ILC1s). Deletion reduces IL-2Rα on ILC1s downregulating NF-κB signaling, thus impairing ILC1 proliferation and cytotoxicity vitro vivo. The binding anti-NKp46 antibody to triggers the activation NF-κB, expression IL-2Rα, interferon-γ (IFN-γ), tumor necrosis factor (TNF), proliferation, cytotoxicity. Functionally, expressed mouse interacts with through cell-cell contact, increasing production IFN-γ TNF, enhancing In model acute myeloid leukemia, deletion impairs ability control growth survival. This can be reversed injecting NKp46+ into knock-out mice. Human exhibit stronger cytokine than their NKp46- counterparts, suggesting plays similar role humans. These findings identify an NKp46-NF-κB-IL-2Rα axis suggest activating may provide potential strategy anti-tumor immunity.

Language: Английский

Citations

0
Helper ILCs in the human hematopoietic system DOI
Xiaoyu Su, Zhaoqun Deng, Yu Lan

et al.

Trends in Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Research progress and development potential of oncolytic vaccinia virus DOI Creative Commons
Xinyu Zhang, Jiangshan He, Yiming Shao

et al.

Chinese Medical Journal, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Abstract Oncolytic virotherapy is a promising therapeutic approach treating tumors, where oncolytic viruses (OVs) can selectively infect and lyse tumor cells through replication, while also triggering long-lasting anti-tumor immune responses. Vaccinia virus (VV) has emerged as leading candidate for use an OV due to its broad cytophilicity robust capacity express exogenous genes. Consequently, vaccinia (OVV) entered clinical trials. This review provides overview of the key strategies used in development OVV, summarizes findings from trials, addresses challenges that must be overcome advancement OVV-based therapies. Furthermore, it explores potential future enhancing application intending improve treatment outcomes. The aims facilitate further adoption thereby advancing

Language: Английский

Citations

0
Catch-to-Amplify Nanoparticles with Bacteria Surface for Sequential Mucosal Immune Activation for Acute Myeloid Leukemia Therapy DOI
Xiaofei Xin, Di Wu, Pengbo Zhao

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Mucosal-mediated immune deficiency is associated with evasion and poor clinical outcomes in acute myeloid leukemia (AML). Here, we describe the elicitation of mucosal systemic response by oral delivery MDP-modified PEG-lipid (MDP-PEG-DSPE) polylactic acid-polyhistidine (PLA-PHis) copolymer constructed nanosystem (mPOD) into Peyer's patches. To protect against gastrointestinal degradation, enteric-soluble capsules are utilized for encapsulating mPOD to promote penetration across intestinal mucus engender robust patch targeting initiated MDP-PEG-DSPE. Compared intravenous intramuscular administration, MDP-PEG-DSPE 5'-triphosphate-modified RNA (ppp-RNA) gut-associated lymphoid tissues reinforces dendritic cell maturation migration, amplifies response, boosts production secretory immunoglobulin A via retinoic acid-inducible gene I/nucleotide-binding oligomerization domain 2 (RIG-I/NOD2) signaling activation. In AML murine model, provoked immunity positively regulates cytotoxic reactions, which, turn, eradicate disseminated malignant leukemic cells provide defense attacks.

Language: Английский

Citations

0
The impact of a single HIIT intervention on the mobilization of NK cells and ILCs in adolescents and young adults (AYA) undergoing cancer treatment: an interventional controlled trial DOI Creative Commons

Isabella Deppe,

Ronja Beller,

Fabian Kiehl

et al.

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 14, 2025

Language: Английский

Citations

0