Transcription factor KLF2 is associated with the dysfunctional status of NK cells and the prognosis of pediatric B-ALL patients DOI Creative Commons

Fang Wu,

Huimin Xu,

Zhang Ben-shan

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 21, 2025

Background Natural killer cells, an important component of the innate immune system, can directly recognize and lyse virally infected or transformed cells. However, NK cells fail to restrain growth malignancies, such as B-cell acute lymphoblastic leukemia (B-ALL). The molecular genetics in B-ALL bone marrow microenvironment mechanisms underlying inhibited function at single-cell level remain largely elusive. Methods In this study, we studied frequency absolute number peripheral blood samples collected from 43 healthy volunteers 104 pediatric patients diagnosed Hunan Children’s Hospital. We also analyzed published RNA sequencing (scRNAseq) data normal using unsupervised clustering. Our findings were further validated bulk transcriptomic clinical a cohort 139 samples. Results found that significantly decreased patients. In-depth analysis scRNAseq identified 12 cell clusters. Among them, C2 cluster, which is present but reduced marrow, displays overexpression transcription factor KLF2 significant downregulation “leukocyte proliferation” pathway. Furthermore, expression diagnosis was positively correlated with percentage positive rate minimal residual disease (MRD), indicating marker poor prognosis. Conclusion There are dramatic differences transcriptomics between donors A factor, KLF2, enriched cluster has been suggested regulate proliferation associated prognosis B-ALL.

Language: Английский

Natural killer cell therapies DOI
Éric Vivier, Lucas Rebuffet, Émilie Narni-Mancinelli

et al.

Nature, Journal Year: 2024, Volume and Issue: 626(8000), P. 727 - 736

Published: Feb. 21, 2024

Language: Английский

Citations

140
γδ T cells: origin and fate, subsets, diseases and immunotherapy DOI Creative Commons
Yi Hu,

Qinglin Hu,

Yongsheng Li

et al.

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

Published: Nov. 22, 2023

The intricacy of diseases, shaped by intrinsic processes like immune system exhaustion and hyperactivation, highlights the potential renormalization as a promising strategy in disease treatment. In recent years, our primary focus has centered on γδ T cell-based immunotherapy, particularly pioneering use allogeneic Vδ2

Language: Английский

Citations

111
Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions DOI Creative Commons

Peilin Lu,

Dongxue Ruan,

Meiqi Huang

et al.

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

Published: July 1, 2024

The applications of hydrogels have expanded significantly due to their versatile, highly tunable properties and breakthroughs in biomaterial technologies. In this review, we cover the major achievements potential therapeutic applications, focusing primarily on two areas: emerging cell-based therapies promising non-cell modalities. Within context cell therapy, discuss capacity overcome existing translational challenges faced by mainstream therapy paradigms, provide a detailed discussion advantages principal design considerations for boosting efficacy as well list specific examples different disease scenarios. We then explore drug delivery, physical intervention therapies, other areas (e.g., bioadhesives, artificial tissues, biosensors), emphasizing utility beyond mere delivery vehicles. Additionally, complement our latest progress clinical application outline future research directions, particularly terms integration with advanced biomanufacturing This review aims present comprehensive view critical insights into selection both tailored meet requirements diverse diseases situations.

Language: Английский

Citations

83
Forks in the road for CAR T and CAR NK cell cancer therapies DOI
Oula K. Dagher, Avery D. Posey

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(12), P. 1994 - 2007

Published: Nov. 27, 2023

Language: Английский

Citations

57
CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors DOI Creative Commons
Lei Peng, Giacomo Sferruzza,

Luojia Yang

et al.

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(10), P. 1089 - 1108

Published: Aug. 12, 2024

Abstract In the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers, demonstrating remarkable efficacy in relapsed/refractory hematological malignancies both pediatric and adult patients. CAR-natural killer (CAR-NK) complements CAR-T by offering several distinct advantages. CAR-NK cells do not require HLA compatibility exhibit low safety concerns. Moreover, are conducive to “off-the-shelf” therapeutics, providing significant logistic advantages over cells. Both have shown consistent results malignancies. However, their against solid tumors remains limited due various obstacles including tumor trafficking infiltration, well an immuno-suppressive microenvironment. this review, we discuss recent advances current challenges of immunotherapies, with specific focus on application tumors. We also analyze depth drawbacks compared highlight CAR optimization. Finally, explore future perspectives these adoptive highlighting increasing contribution cutting-edge biotechnological tools shaping next generation cellular immunotherapy.

Language: Английский

Citations

32
Advancing Natural Killer Cell Therapy: Genetic Engineering Strategies for Enhanced Cancer Immunotherapy DOI Open Access
Joo Dong Park, Ha Eun Shin,

Y. An

et al.

Annals of Laboratory Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Joo Dong Park, M.S., Ha Eun Shin, Ph.D., Yeon Su An, B.S., Hye Jung Jang, Juwon Se-Na Kim, Chun Gwon and Wooram Ph.D.. Ann Lab Med -0001;0:. https://doi.org/10.3343/alm.2024.0380

Citations

2
Chimeric antigen receptor engineered natural killer cells for cancer therapy DOI Creative Commons
Yalan Zhang, Weilin Zhou, Jianping Yang

et al.

Experimental Hematology and Oncology, Journal Year: 2023, Volume and Issue: 12(1)

Published: Aug. 10, 2023

Abstract Natural killer (NK) cells, a unique component of the innate immune system, are inherent killers stressed and transformed cells. Based on their potent capacity to kill cancer cells good tolerance healthy NK have been successfully employed in adoptive cell therapy treat patients. In recent years, clinical success chimeric antigen receptor (CAR)-T has proven vast potential gene-manipulated as main force fight cancer. Following lessons learned from mature gene-transfer technologies advanced strategies CAR-T therapy, rapidly explored promising candidate for CAR-based therapy. An exponentially growing number studies multiple sources CAR-NK target wide range cancer-related antigens, showing remarkable outcomes encouraging safety profiles. Clinical trials also shown impressive therapeutic efficacy treatment hematological tumors, but solid tumors is still initial stages. this review, we present favorable profile platform engineering then summarize therapies up-to-date preclinical investigations. Finally, evaluate challenges remaining describe existing that can assist us devising future prospective solutions.

Language: Английский

Citations

29
T-BET and EOMES sustain mature human NK cell identity and antitumor function DOI Creative Commons
Pamela Wong, Jennifer A. Foltz, Lily Chang

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(13)

Published: June 6, 2023

Since T-box transcription factors (TFs) T-BET and EOMES are necessary for initiation of NK cell development, their ongoing requirement mature homeostasis, function, molecular programming remains unclear. To address this, were deleted in unexpanded primary human cells using CRISPR/Cas9. Deleting these TFs compromised vivo anti-tumor response cells. Mechanistically, required normal proliferation persistence vivo. lacking also exhibited defective responses to cytokine stimulation. Single-cell RNA-sequencing revealed a specific transcriptional program cells, which was rapidly lost following deletion. Further, CD56bright acquired an ILCP-like profile with increased expression ILC-3-associated RORC AHR, revealing role TF maintaining phenotypes unexpected suppressing alternative ILC lineages. Our study reveals the critical importance sustained orchestrate function identity.

Language: Английский

Citations

27
Natural Killer Cell-Based Immunotherapy against Glioblastoma DOI Open Access
Takayuki Morimoto, Tsutomu Nakazawa, Ryosuke Maeoka

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2111 - 2111

Published: Jan. 20, 2023

Glioblastoma (GBM) is the most aggressive and malignant primary brain tumor in adults. Despite multimodality treatment involving surgical resection, radiation therapy, chemotherapy, tumor-treating fields, median overall survival (OS) after diagnosis approximately 2 years 5-year OS poor. Considering poor prognosis, novel strategies are needed, such as immunotherapies, which include chimeric antigen receptor T-cell immune checkpoint inhibitors, vaccine oncolytic virus therapy. However, these therapies have not achieved satisfactory outcomes. One reason for this that mainly based on activating T cells controlling GBM progression. Natural killer (NK) cell-based immunotherapy involves new feature of recognizing via differing mechanisms from immunotherapy. In review, we focused NK a strategy.

Language: Английский

Citations

25
CAR-T cell therapy for hematological malignancies: History, status and promise DOI Creative Commons
Chao Wang, Jianpeng Wang, Shusheng Che

et al.

Heliyon, Journal Year: 2023, Volume and Issue: 9(11), P. e21776 - e21776

Published: Nov. 1, 2023

For many years, the methods of cancer treatment are usually surgery, chemotherapy and radiation therapy. Although these help to improve condition, most tumors still have a poor prognosis. In recent immunotherapy has great potential in tumor treatment. Chimeric antigen receptor T-cell (CAR-T) uses patient's own T cells express chimeric receptors. (CAR) recognizes tumor-associated antigens kills cells. CAR-T achieved good results hematological tumors. 2017, FDA approved first for B-cell acute lymphoblastic leukemia (ALL). October same year, treat lymphoma. order enhance therapeutic effect, become research focus years. The structure CAR, targets treatment, adverse reactions improvement measures during process summarized. This review is an attempt highlight possibly forgotten findings advances cell

Language: Английский

Citations

24