A Dual Stimuli-Responsive Nanoimmunomodulator for Antitumor Synergy of Macrophages and T Cells DOI

Jun‐Ying Ding,

Xueze Zhao,

Saran Long

et al.

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

Published: Feb. 7, 2025

Only a minority of patients benefit from current T-cell-focused adaptive immunotherapies, underscoring the need to engage innate immune cells, particularly macrophages, for multilayered tumor control. However, high-efficacy therapeutics capable orchestrating multiple cells remain scarce. Herein, dual stimuli-responsive nanoimmunomodulator (6EPP@si) that caters specifically microenvironment (TME) is presented antitumor synergy macrophages and T cells. Using functional polymer-based carrier, we co-deliver endoplasmic reticulum (ER)-localized photosensitizer 6E small interfering RNA targeting CD47 (siCD47) into breast tumors. Within acidic high-glutathione TME, 6EPP@si undergoes self-lysosome escape nanocleavage precise, on-demand drug release. Consequently, siCD47 released cytoplasm enables potent silencing, while ER-targeted induces immunogenic cell death through reactive oxygen species-based ER stress, triggering release damage-associated molecular patterns, including calreticulin surface translocation. enhances macrophage phagocytosis by modulating both antiphagocytic prophagocytic signals also promotes antigen presentation activate In orthotopic spontaneous lung metastatic models, this combined approach demonstrates robust effects effective antimetastatic immunity, offering meaningful strategy simultaneously enhancing cancer immunotherapy.

Language: Английский

Targeting cytokine and chemokine signaling pathways for cancer therapy DOI Creative Commons
Ming Yi, Tianye Li,

Mengke Niu

et al.

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

Published: July 22, 2024

Abstract Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles both normal physiology the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, growth factors like TGF-β, VEGF, EGF, can promote or inhibit growth, influence microenvironment, impact efficacy cancer treatments. Recent advances targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate system, progression, overcome resistance conventional therapies. In this review, we summarized current understanding implications cytokine chemokine signaling By exploring molecules biology response, highlighted development novel agents aimed at modulating combat The review elaborated on nature cytokines promoters suppressors tumorigenesis, depending context, discussed challenges opportunities presents for intervention. We also examined latest advancements targeted therapies, monoclonal antibodies, bispecific receptor inhibitors, fusion proteins, engineered variants, their metastasis, microenvironment. Additionally, evaluated potential combining therapies with other treatment modalities improve patient outcomes. Besides, focused ongoing research clinical trials that pivotal advancing our application cytokine- chemokine-targeted patients.

Language: Английский

Citations

50
CAR-NK cells for cancer immunotherapy: recent advances and future directions DOI Creative Commons
Tianye Li,

Mengke Niu,

Weijiang Zhang

et al.

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

Published: Feb. 9, 2024

Natural Killer (NK) cells, intrinsic to the innate immune system, are pivotal in combating cancer due their independent cytotoxic capabilities antitumor response. Unlike predominant treatments that target T cell immunity, limited success of immunotherapy emphasizes urgency for innovative approaches, with a spotlight on harnessing potential NK cells. Despite tumors adapting mechanisms evade cell-induced cytotoxicity, there is optimism surrounding Chimeric Antigen Receptor (CAR) This comprehensive review delves into foundational features and recent breakthroughs comprehending dynamics cells within tumor microenvironment. It critically evaluates applications challenges associated emerging CAR-NK therapeutic strategies, positioning them as promising tools evolving landscape precision medicine. As research progresses, unique attributes offer new avenue interventions, paving way more effective precise approach treatment.

Language: Английский

Citations

23
Hallmarks of cancer resistance DOI Creative Commons
Muhammad Tufail,

Jia-Ju Hu,

Jie Liang

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 109979 - 109979

Published: May 15, 2024

This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized Warburg effect, and dynamic interplay between cells mitochondria. The role stem (CSCs) in treatment resistance regulatory influence non-coding RNAs, such as long RNAs (lncRNAs), microRNAs (miRNAs), circular (circRNAs), are studied. chapter emphasizes future directions, encompassing advancements immunotherapy, strategies to counter adaptive integration artificial intelligence for predictive modeling, identification biomarkers personalized treatment. comprehensive exploration these provides a foundation innovative therapeutic approaches, aiming navigate complex landscape enhance patient outcomes.

Language: Английский

Citations

18
The interaction of innate immune and adaptive immune system DOI Creative Commons

Ruyuan Wang,

Caini Lan, Kamel Benlagha

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(10)

Published: Sept. 15, 2024

The innate immune system serves as the body's first line of defense, utilizing pattern recognition receptors like Toll-like to detect pathogens and initiate rapid response mechanisms. Following this initial response, adaptive immunity provides highly specific sustained killing via B cells, T antibodies. Traditionally, it has been assumed that activates immunity; however, recent studies have revealed more complex interactions. This review a detailed dissection composition function systems, emphasizing their synergistic roles in physiological pathological contexts, providing new insights into link between these two forms immunity. Precise regulation both systems at same time is beneficial fight against immune-related diseases, for example, cGAS-STING pathway found play an important role infections cancers. In addition, paper summarizes challenges future directions field immunity, including latest single-cell sequencing technologies, CAR-T cell therapy, checkpoint inhibitors. By summarizing developments, aims enhance our understanding complexity interactions perspectives system.

Language: Английский

Citations

15
The enhanced antitumor activity of bispecific antibody targeting PD-1/PD-L1 signaling DOI Creative Commons
Tianye Li,

Mengke Niu,

Jianwei Zhou

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 12, 2024

Abstract The programmed cell death 1 (PD-1) signaling pathway, a key player in immune checkpoint regulation, has become focal point cancer immunotherapy. In the context of cancer, upregulated PD-L1 on tumor cells can result T exhaustion and evasion, fostering progression. advent PD-1/PD-L1 inhibitor demonstrated clinical success by unleashing from exhaustion. Nevertheless, challenges such as resistance adverse effects have spurred exploration innovative strategies, with bispecific antibodies (BsAbs) emerging promising frontier. BsAbs offer multifaceted approach to immunotherapy simultaneously targeting other regulatory molecules. We focus recent advancements therapy particular emphasis development potential BsAbs, especially solid tumors. Various BsAb products PD-1 are discussed, highlighting their unique mechanisms action therapeutic potential. Noteworthy examples include anti-TGFβ × PD-L1, anti-CD47 anti-VEGF anti-4-1BB anti-LAG-3 anti-PD-1 CTLA-4 BsAbs. Besides, we summarize ongoing studies evaluating efficacy safety these agents. By unraveling intricacies microenvironment harnessing synergistic anti-PD-1/PD-L1 there exists elevate precision immunotherapy, ultimately enabling personalized treatment strategies tailored individual patient profiles.

Language: Английский

Citations

14
Metabolic reprogramming and immune evasion: the interplay in the tumor microenvironment DOI Creative Commons
Haixia Zhang, Shizhen Li, Dan Wang

et al.

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Sept. 3, 2024

Abstract Tumor cells possess complex immune evasion mechanisms to evade system attacks, primarily through metabolic reprogramming, which significantly alters the tumor microenvironment (TME) modulate cell functions. When a is sufficiently immunogenic, it can activate cytotoxic T-cells target and destroy it. However, tumors adapt by manipulating their pathways, particularly glucose, amino acid, lipid metabolism, create an immunosuppressive TME that promotes escape. These alterations impact function differentiation of non-tumor within TME, such as inhibiting effector T-cell activity while expanding regulatory myeloid-derived suppressor cells. Additionally, these changes lead imbalance in cytokine chemokine secretion, further enhancing landscape. Emerging research increasingly focusing on roles evaluating how reprogrammed metabolism influence functional ultimately aid evasion. Despite our incomplete understanding intricate interactions between cells, connection elements presents significant challenges for cancer immunotherapy. This review highlights altered providing new insights could facilitate development novel immunotherapies.

Language: Английский

Citations

14
Autophagy in cancer immunotherapy: Perspective on immune evasion and cell death interactions DOI
Qiang Yu,

Jiajun Ding,

Shisen Li

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 590, P. 216856 - 216856

Published: April 5, 2024

Language: Английский

Citations

9
Oncometabolite 2-hydroxyglutarate regulates anti-tumor immunity DOI Creative Commons
Mengyuan Cai, Jianyi Zhao, Qiang Ding

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(2), P. e24454 - e24454

Published: Jan. 1, 2024

"Oncometabolite" 2-hydroxyglutarate (2-HG) is an aberrant metabolite found in tumor cells, exerting a pivotal influence on progression. Recent studies have unveiled its impact the proliferation, activation, and differentiation of anti-tumor T cells. Moreover, 2-HG regulates function innate immune components, including macrophages, dendritic natural killer complement system. Elevated levels hinder α-KG-dependent dioxygenases (α-KGDDs), contributing to tumorigenesis by disrupting epigenetic regulation, genome integrity, hypoxia-inducible factors (HIF) signaling, cellular metabolism. The chiral molecular structure produces two enantiomers: D-2-HG L-2-HG, each with distinct origins biological functions. Efforts inhibit leverage potential L-2-HG demonstrated efficacy cancer immunotherapy. This review delves into metabolism, functions, impacts microenvironment (TIME) 2-HG, providing comprehensive exploration intricate relationship between antitumor immunity. Additionally, we examine clinical applications targeted therapy for highlighting recent breakthroughs as well existing challenges.

Language: Английский

Citations

8
Beyond success: unveiling the hidden potential of radiotherapy and immunotherapy in solid tumors DOI Creative Commons
Yuze Wu, Ming Yi,

Mengke Niu

et al.

Cancer Communications, Journal Year: 2024, Volume and Issue: 44(7), P. 739 - 760

Published: June 5, 2024

Abstract Immunotherapy, particularly with immune checkpoint inhibitors, has significantly transformed cancer treatment. Despite its success, many patients struggle to respond adequately or sustain long‐lasting clinical improvement. A growing consensus emerged that radiotherapy (RT) enhances the response rate and overall efficacy of immunotherapy. Although combining RT immunotherapy been extensively investigated in preclinical models shown promising results, establishing itself as a dynamic thriving area research, evidence for this combination strategy over past five years both positive disappointing suggesting need more nuanced understanding. This review provides balanced updated analysis RT. We summarized mechanisms through which boosts antitumor responses mainly focused on outcomes recently trials, including those may not have met expectations. optimization therapeutic potential combined strategy, key challenges, such fractionation scheduling, lymph node irradiation, toxicity. Finally, we offered insights into prospects challenges associated translation therapy, providing realistic perspective current state research future directions.

Language: Английский

Citations

8
Innate Immune Cells in Tumour Microenvironment: A New Frontier in Cancer Immunotherapy DOI Creative Commons
Changhui Li, Xinyu Yu, Xinyan Han

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(9), P. 110750 - 110750

Published: Aug. 17, 2024

Innate immune cells, crucial in resisting infections and initiating adaptive immunity, play diverse significant roles tumor development. These including macrophages, granulocytes, dendritic cells (DCs), innate lymphoid innate-like T are pivotal the microenvironment (TME). components of TME, based on which various immunotherapy strategies have been explored. Immunotherapy strategies, such as novel checkpoint inhibitors, STING/CD40 agonists, macrophage-based surface backpack anchoring,

Language: Английский

Citations

8