Immune dynamics shaping pre-metastatic and metastatic niches in liver metastases: from molecular mechanisms to therapeutic strategies DOI Creative Commons
Chang Zhu,

J Liao,

Yiyang Liu

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Nov. 14, 2024

Liver metastases are commonly detected in the advanced stages of various malignant tumors, representing a significant clinical challenge. Throughout process liver formation, immune cells play pivotal role, particularly pre-metastatic and metastatic niches within liver. Immune establish extensive intricate interactions with tumor other components liver, collectively promoting sustaining growth metastases. Despite limited efficacy existing therapeutic modalities against some metastases, novel immune-based treatment approaches continuously being explored validated. Building on systematic elucidation immunosuppressive characteristics we potential immunotherapies applicable to patients from multiple dimensions.

Language: Английский

Advances in Radionuclide-Labeled Biological Carriers for Tumor Imaging and Treatment DOI
Yaozhang Yang, Jing Wang,

Yan Zhong

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Biological carriers have emerged as significant tools to deliver radionuclides in nuclear medicine, providing a meaningful perspective for tumor imaging and treatment. Various radionuclide-labeled biological been developed meet the needs of biomedical applications. This review introduces principles radionuclide-mediated therapy selected criteria them, well comprehensive description characteristics functions representative including bacteria, cells, viruses, their derivatives, emphasizing labeled strategies combined with radionuclides. Subsequently, we in-depth introduce application treatment, behaviors vivo metastasis treatment by radionuclide therapy, plus other radiation-induced photodynamic therapy. Finally, challenges prospects are discussed improve shortcomings this innovative platform promote clinical transformation field medical imaging.

Language: Английский

Citations

1

Pan-caspase inhibitors induce secretion of HIV-1 latency reversal agent lymphotoxin-alpha from cytokine-primed NK cells DOI Creative Commons
Zamaneh Hajikhezri, Ioannis Zygouras, Anders Sönnerborg

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 4, 2025

The persistence of HIV-1 latency reservoirs in CD4+ T cells is a significant obstacle for curing HIV-1. Shock-and-kill strategies, which aim to reactivate latent followed by cytotoxic clearance, have shown limited success vivo due insufficient efficacy reversal agents (LRAs) and off-target effects. Natural killer (NK) cells, with their ability mediate cytotoxicity independent antigen specificity, offer promising avenue enhancing the shock-and-kill approach. Previously, we observed that pan-caspase inhibitors induce NK secrete an LRA vitro. Here, aimed identify this using targeted proteomic We identified lymphotoxin-α (LTα) as key secreted following inhibitor treatment. LTα was significantly LTR promoter activity, hallmark viral reactivation. Neutralization effectively abolished confirming its central role. Moreover, cytokine-primed but not resting human primary exhibited activity could be neutralized neutralizing antibodies. Finally, treatment did decrease kill target cells. These findings demonstrate through secretion, can treatment, without compromising cell cytotoxicity. This highlights potential enhancement strategy utilizing approaches cure research.

Language: Английский

Citations

1

Enhancing NK Cell Antitumor Activity With Natural Compounds: Research Advances and Molecular Mechanisms DOI Open Access

Yu Wu,

Mingxiao Yin,

Wenjiao Xia

et al.

Phytotherapy Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

In recent years, immunotherapy has become a novel antitumor strategy in addition to traditional surgery, radiotherapy, and chemotherapy exhibited promising results clinical applications. Despite significant breakthroughs immunotherapy, such as immune checkpoint blockade CAR-T cell therapy, it remains necessary develop more efficacious, safer, cheaper immunotherapeutic drugs due factors including small reaction populations, acquired resistance, adverse side effects, high costs. Natural killer (NK) cells are preeminent cytotoxic lymphocytes of the innate system that act first line defense against tumors synergistically enhance adaptive response T lymphocytes. Therefore, boosting function NK is an important direction development immunotherapy. For decades, various immunotherapies adoptive antibody drugs, cytokines supplement, chemical immunomodulators have been developing rapidly improve cells. Compared biological derived from natural products outstanding advantages low immunogenicity, multi-targeting, cost-effectiveness. Currently, increasing attention being focused on discovering cell-stimulating agents products, polysaccharides, alkaloids, terpenoids, saponins, phenolics, quinones. This review aims categorize summarize comprehensive research progress these discuss their potential molecular mechanisms regulating cells, explore applications standalone treatments or combination with conventional regimens.

Language: Английский

Citations

1

Are monocytes a preferable option to develop myeloid cell-based therapies for solid tumors? DOI Creative Commons

Daisy Bhatia,

Riccardo Dolcetti, Roberta Mazzieri

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: March 15, 2025

Abstract In the last two decades, novel and promising cell-based therapies have populated treatment landscape for haematological tumors. However, commonly exploited T NK show limited applicability to solid This is mainly given by impaired tumor trafficking capability effector activity of these cells within a highly immunosuppressive microenvironment. Myeloid spontaneously home tumors can thus be reprogrammed and/or engineered directly attack or locally selectively deliver therapeutically relevant payloads that may improve efficacy immunotherapy against difficult-to-access context myeloid therapies, adoptive transfer monocytes has often been overshadowed infusion differentiated macrophages hematopoietic stem cell transplantation despite their therapeutic potential. Here, we summarize recent improvements benefits using tumors, current clinical applications challenges use as well some possible strategies overcome them.

Language: Английский

Citations

1

Human NK cells and cancer DOI Creative Commons
Claudia Cantoni, Michela Falco, Massimo Vitale

et al.

OncoImmunology, Journal Year: 2024, Volume and Issue: 13(1)

Published: July 16, 2024

The long story of NK cells started about 50 y ago with the first demonstration a natural cytotoxic activity within an undefined subset circulating leukocytes, has involved ever-growing number researchers, fascinated by apparently easy-to-reach aim getting "universal anti-tumor immune tool". In fact, in spite impressive progress obtained decades, these proved far more complex than expected and, paradoxically, accumulating findings have continuously moved forward attainment complete control their function for immunotherapy. refined studies latter years indicated that can epigenetically calibrate functional potential, response to specific environmental contexts, giving rise extraordinarily variegated subpopulations, comprehensive memory-like cells, tissue-resident or various differentiation stages, distinct states. addition, adapt body signals, spanning from interaction either suppressive stimulating (myeloid-derived suppressor dendritic respectively) engagement receptors (specific checkpoints, cytokines, tumor/viral ligands, mediating antibody-dependent cell-mediated cytotoxicity). According this picture, idea easy and generalized exploitation is changing, way opening toward new carefully designed, combined personalized therapeutic strategies, also based on use genetically modified stimuli capable strengthening redirecting effector functions against cancer.

Language: Английский

Citations

7

Natural killer cells in cancer immunotherapy DOI Creative Commons
Danru Wang,

LingYun Dou,

Lihao Sui

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(7)

Published: June 15, 2024

Natural killer (NK) cells, as innate lymphocytes, possess cytotoxic capabilities and engage target cells through a repertoire of activating inhibitory receptors. Particularly, natural group 2, member D (NKG2D) receptor on NK recognizes stress-induced ligands-the MHC class I chain-related molecules A B (MICA/B) presented tumor is key to trigger the cytolytic response cells. However, tumors have developed sophisticated strategies evade cell surveillance, which lead failure immunotherapy. In this paper, we summarized these immune escaping strategies, including downregulation ligands for receptors, upregulation secretion immunosuppressive compounds, development apoptosis resistance. Then, focus recent advancements in therapies, include engaging upregulating NKG2D ligand MICA/B expression, blocking adoptive therapy, chimeric antigen (CAR)-engineered (CAR-NK), CAR-T especially several vaccines targeting MICA/B. This review will inspire research biology provide significant hope improving cancer treatment outcomes by harnessing potent activity

Language: Английский

Citations

6

Therapeutic effect of small extracellular vesicles from cytokine-induced memory-like natural killer cells on solid tumors DOI Creative Commons
Ying‐Hong Shi, Yanxia Chen, Yi Wang

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 29, 2024

Abstract Small extracellular vesicles (sEV) derived from diverse natural killer (NK) cell lines have proven their exceptional antitumor activities. However, sEV human primary NK cells, especially memory-like are rarely utilized for cancer treatment. In this study, we obtained IL-12, IL-15 and IL-18 cultured cells (mNK-sEV) that showed strong cytokine-secretory ability. It was uncovered mNK-sEV entered via macropinocytosis induced apoptosis caspase-dependent pathway. Compared to conventionally (conNK-sEV), inhibited tumor growth a greater extent. Concomitantly, pharmacokinetics biodistribution results validated higher accumulation of than conNK-sEV in tumors xenografted murine models. Notably, elevated containment granulysin (GNLY) within mNK-sEV, at least part, may contribute the enhanced therapeutic effect. Herein our present can be novel class reagent effective Graphical

Language: Английский

Citations

6

Immunocytes interact directly with cancer cells in the tumor microenvironment: one coin with two sides and future perspectives DOI Creative Commons
Zhiyi Ye, Pu Cheng, Qi Huang

et al.

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

Published: May 22, 2024

The tumor microenvironment is closely linked to the initiation, promotion, and progression of solid tumors. Among its constitutions, immunologic cells emerge as critical players, facilitating immune evasion progression. Apart from their indirect impact on anti-tumor immunity, immunocytes directly influence neoplastic cells, either bolstering or impeding advancement. However, current therapeutic modalities aimed at alleviating immunosuppression regulatory effector cell populations may not consistently yield satisfactory results in various tumors, such breast carcinoma, colorectal cancer, etc. Therefore, this review outlines summarizes direct, dualistic effects T innate lymphoid B eosinophils, tumor-associated macrophages within microenvironment. also delves into underlying mechanisms involved presents outcomes clinical trials based these direct effects, aiming propose innovative efficacious strategies for addressing

Language: Английский

Citations

5

Advances in CAR-NK cell therapy for hematological malignancies DOI Creative Commons
Rui Yang,

Yun Yang,

Rui Liu

et al.

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

Published: June 28, 2024

Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of hematological malignancies, demonstrably improving patient outcomes and prognosis. However, its application introduced new challenges, such as safety concerns, off-target toxicities, significant costs. Natural killer (NK) cells are crucial components innate immune system, capable eliminating tumor without prior exposure to specific antigens or pre-activation. This inherent advantage complements limitations cells, making CAR-NK a promising avenue for immunotherapy. In recent years, preclinical clinical studies have yielded preliminary evidence supporting efficacy in paving way future advancements review aims succinctly discuss characteristics, therapeutic progress, potential challenges associated with therapy.

Language: Английский

Citations

5

Designable Nanoadaptor for Enhanced Recognition of Natural Killer Cell to Tumor via Bio-orthogonal Click Reaction DOI
Xiaohu Yang, Hongchao Yang, Tuanwei Li

et al.

Nano Letters, Journal Year: 2024, Volume and Issue: 24(25), P. 7698 - 7705

Published: June 13, 2024

Highly efficient recognition of cancer cells by immune is important for successful therapeutic-cell-based immunotherapy. Herein, we present a facile NIR-II nanoadaptor [hyaluronic acid (HA)/dibenzocyclooctyne (DBCO)-Au:Ag2Te quantum dots (QDs)] enhancing the tumor and binding ability natural killer (NK) via bio-orthogonal click reaction in vivo. The Nanoadaptor possesses superior tumor-targeting capacity, facilitating accumulation chemical receptor DBCO at sites. Subsequently, enrichment on cell surfaces provides multivalent sites capturing pretreated azide engineered NK92 (NK92-N3) through an reaction, thereby significantly therapeutical efficiency. dynamic process nanoadaptor-mediated NK to could be vividly observed using multiplexed fluorescence imaging mouse model lung cancer. Such strategy can extended other therapeutic cellular systems holds promise future clinical applications.

Language: Английский

Citations

4