Targeting PI3K-gamma in myeloid driven tumour immune suppression: a systematic review and meta-analysis of the preclinical literature DOI Creative Commons
Haonan Xu,

Shannon Nicole Russell,

Katherine Steiner

et al.

Cancer Immunology Immunotherapy, Journal Year: 2024, Volume and Issue: 73(10)

Published: Aug. 6, 2024

Abstract The intricate interplay between immune and stromal cells within the tumour microenvironment (TME) significantly influences progression. Myeloid cells, including tumour-associated macrophages (TAMs), neutrophils (TANs), myeloid-derived suppressor (MDSCs), contribute to suppression in TME (Nakamura Smyth Cell Mol Immunol 17(1):1–12 (2020). https://doi.org/10.1038/s41423-019-0306-1 ; DeNardo Ruffell Nat Rev 19(6):369–382 (2019). https://doi.org/10.1038/s41577-019-0127-6 ). This poses a significant challenge for novel immunotherapeutics that rely on host immunity exert their effect. systematic review explores preclinical evidence surrounding inhibition of phosphoinositide 3-kinase gamma (PI3Kγ) as strategy reverse myeloid-driven solid tumours. EMBASE, MEDLINE, PubMed databases were searched 6 October 2022 using keyword subject heading terms capture relevant studies. studies, focusing PI3Kγ animal models, subjected predefined inclusion exclusion criteria. Extracted data included growth kinetics, survival endpoints, immunological responses which meta-analysed. PRISMA MOOSE guidelines followed. A total 36 studies covering 73 models meta-analysis. Tumour covered breast, colorectal, lung, skin, pancreas, brain, liver, prostate, head neck, soft tissue, gastric, oral cancer. predominant inhibitors IPI-549 TG100-115, demonstrating favourable specificity isoform. Combination therapies, often involving chemotherapy, radiotherapy, checkpoint inhibitors, biological agents, or vaccines, explored 81% Analysis kinetics revealed statistically though heterogeneous response monotherapy, whereas combination treated groups more consistently reduced. Survival analysis showed pronounced increase median overall with therapy. provides comprehensive investigating suppression. identified underscore potential reshaping by modulating myeloid cell functions. other therapeutic modalities demonstrated enhanced antitumour effects, suggesting synergistic approach overcome These findings support PI3Kγ-targeted particularly regimens, promising avenue future clinical exploration diverse types. Graphical abstract

Language: Английский

Nanomaterials for bone metastasis DOI

Xinyan Hao,

Buchan Jiang,

Junyong Wu

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 373, P. 640 - 651

Published: Aug. 1, 2024

Language: Английский

Citations

36
Leveraging Aptamer-Based DNA Nanotechnology for Bioanalysis and Cancer Therapeutics DOI Creative Commons
Zhiyong Huang, Dan Wang, Qiang Zhang

et al.

Accounts of Materials Research, Journal Year: 2024, Volume and Issue: 5(4), P. 438 - 452

Published: March 14, 2024

ConspectusAptamers are single-stranded DNA or RNA molecules composed of 15–80 nucleotides, obtained from a random oligonucleotide library via the systematic evolution ligands by exponential enrichment (SELEX) technology. They can bind to wide range targets with high binding affinity and specificity including metal ions, small molecules, proteins, cells, even tissues. When compared commonly used antibodies, aptamers show better thermal stability, smaller molecular weight, easier modification, little batch-to-batch variation chemical synthesis. These unique merits position as promising tools in biomedical applications, spanning biosensing, bioimaging, disease diagnosis, targeted chemotherapy, cancer immunotherapy. However, chemically synthesized oligonucleotides, would be degraded nucleic acid degrading enzymes (e.g., endonucleases exonucleases) presented blood circulation, thereby reducing stability activity. Another limitation is rapid clearance liver kidneys, their circulation life bioavailability. Recent progress nanotechnology has garnered global interest, emerging interdisciplinary applications across chemistry, materials, biology, medicine. The fundamental self-assemblies dynamic operation Watson–Crick base pairing assisted silico programmable design. As functional building blocks, inherently enable great potential bioanalysis, drug delivery, Therefore, aptamer-based arouse important interests future research.As medicine offered personalized precise diagnostic therapeutic solutions, this Account, we focus on research advancements leveraging aptamer for medicine, particularly our recent progress. Often referred bioanalysis therapeutics. Thus, two parts discussed Account: initially, discuss modifications cyclization nucleotide backbone engineering. aptamer-tethered nanostructures then were constructed cell identification bioanalysis. To perform intelligent detailed three formulations aptamer-involved computation. In last part, chemotherapy Based covalent coupling strategy, report series conjugates. Similarly, employing circular bivalent conjugates discussed. Next, molecule delivery systems encounter challenges related insufficient biological terms vulnerability enzyme cleavage short time vivo, nanomedicines introduced chemotherapy. immunotherapy section includes tumor vaccines, adoptive immunotherapy, immune checkpoint blockade. Finally, propose opportunities bioapplications nanotechnology.

Language: Английский

Citations

32
Advancing cancer immunotherapy through siRNA-based gene silencing for immune checkpoint blockade DOI Creative Commons
Young‐Jin Choi, Su Hyun Seok, Hong Yeol Yoon

et al.

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 209, P. 115306 - 115306

Published: April 16, 2024

Cancer immunotherapy represents a revolutionary strategy, leveraging the patient's immune system to inhibit tumor growth and alleviate immunosuppressive effects of microenvironment (TME). The recent emergence checkpoint blockade (ICB) therapies, particularly following first approval cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors like ipilimumab, has led significant in cancer immunotherapy. extensive explorations on diverse antibodies have broadened therapeutic scope for various malignancies. However, clinical response these antibody-based ICB therapies remains limited, with less than 15% responsiveness notable adverse some patients. This review introduces emerging strategies overcome current limitations mainly focusing development small interfering ribonucleic acid (siRNA)-based innovative delivery systems. We firstly highlight target genes siRNA-based incorporating silencing multiple boost anti-tumor responses. Subsequently, we discuss improvements siRNA systems, enhanced by nanocarriers, aimed at overcoming siRNA's challenges such as vulnerability enzymatic degradation, inadequate pharmacokinetics, possible unintended interactions. Additionally, presents combination that integrate chemotherapy, phototherapy, stimulatory checkpoints, antibodies, vaccines. important point is when used therapy, synergistic effect traditional strengthened, improving host surveillance outcomes. Conclusively, insights into effective immunotherapeutic based RNA interference (RNAi) technology utilizing nanocarriers novel approach

Language: Английский

Citations

19
EGFR Oncogenic Mutations in NSCLC Impair Macrophage Phagocytosis and Mediate Innate Immune Evasion Through Up-Regulation of CD47 DOI

Liyang Hu,

Weitao Zhuang,

Mao-jian Chen

et al.

Journal of Thoracic Oncology, Journal Year: 2024, Volume and Issue: 19(8), P. 1186 - 1200

Published: March 27, 2024

Language: Английский

Citations

17
Programmed death receptor (PD-)1/PD-ligand (L)1 in urological cancers : the “all-around warrior” in immunotherapy DOI Creative Commons
Qiang Liu,

Yujing Guan,

Shenglong Li

et al.

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

Published: Sept. 2, 2024

Programmed death receptor-1 (PD-1) and its ligand, programmed ligand-1 (PD-L1) are essential molecules that key in modulating immune responses. PD-L1 is constitutively expressed on various cells, epithelial cancer where it functions as a co-stimulatory molecule capable of impairing T-cell mediated Upon binding to PD-1 activated T-cells, the PD-1/PD-L1 interaction triggers signaling pathways can induce apoptosis or anergy, thereby facilitating escape tumors. In urological cancers, including bladder (BCa), renal cell carcinoma (RCC), prostate (PCa), upregulation has been demonstrated. It linked poor prognosis enhanced tumor evasion. Recent studies have highlighted significant role axis mechanisms cancers. The between T-cells further contributes immunosuppression by inhibiting activation proliferation. Clinical applications checkpoint inhibitors shown promising efficacy treating advanced significantly improving patient outcomes. However, resistance these therapies, either intrinsic acquired, remains challenge. This review aims provide comprehensive overview pathway We summarize regulatory mechanism underlying expression activity, genetic, epigenetic, post-transcriptional, post-translational modifications. Additionally, we discuss current clinical research inhibitors, their therapeutic potential, challenges associated with resistance. Understanding crucial for developing new strategies overcome limitations enhance immunotherapy.

Language: Английский

Citations

16
AND-gated protease-activated nanosensors for programmable detection of anti-tumour immunity DOI
Anirudh Sivakumar, Hathaichanok Phuengkham,

Hitha Rajesh

et al.

Nature Nanotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Language: Английский

Citations

2
In Situ Formed Microalgae-Integrated Living Hydrogel for Enhanced Tumor Starvation Therapy and Immunotherapy through Photosynthetic Oxygenation DOI
Cheng Zhang, Ziyi Han, Kewei Chen

et al.

Nano Letters, Journal Year: 2024, Volume and Issue: 24(12), P. 3801 - 3810

Published: March 13, 2024

The effectiveness of various cancer therapies for solid tumors is substantially limited by the highly hypoxic tumor microenvironment (TME). Here, a microalgae-integrated living hydrogel (ACG gel) developed to concurrently enhance hypoxia-constrained starvation therapy and immunotherapy. ACG gel formed in situ following intratumoral injection biohybrid fluid composed alginate, Chlorella sorokiniana, glucose oxidase, facilitated crossing-linking between divalent ions within alginate. microalgae sorokiniana embedded generate abundant oxygen through photosynthesis, enhancing oxidase-catalyzed consumption shifting TME from immunosuppressive immunopermissive status, thus reducing cell energy supply boosting antitumor immunity. In murine 4T1 models, significantly suppresses growth effectively prevents postoperative recurrence. This study, leveraging as natural oxygenerators, provides versatile universal strategy development oxygen-dependent therapies.

Language: Английский

Citations

11
The Complex Tumor Microenvironment in Ovarian Cancer: Therapeutic Challenges and Opportunities DOI Creative Commons
Bianca Garlisi,

Sylvia Lauks,

Caroline Aitken

et al.

Current Oncology, Journal Year: 2024, Volume and Issue: 31(7), P. 3826 - 3844

Published: July 1, 2024

The tumor microenvironment (TME) in ovarian cancer (OC) has much greater complexity than previously understood. In response to aggressive pro-angiogenic stimulus, blood vessels form rapidly and are dysfunctional, resulting poor perfusion, tissue hypoxia, leakiness, which leads increased interstitial fluid pressure (IFP). Decreased perfusion high IFP significantly inhibit the uptake of therapies into tumor. Within TME, there numerous inhibitor cells, such as myeloid-derived suppressor cells (MDSCs), association macrophages (TAMs), regulatory T (Tregs), cancer-associated fibroblasts (CAFs) that secrete numbers immunosuppressive cytokines. This environment is thought contribute lack success immunotherapies immune checkpoint (ICI) treatment. review discusses components TME OC, how these characteristics impede therapeutic efficacy, some strategies alleviate this inhibition.

Language: Английский

Citations

11
YAP1 Inhibition Induces Phenotype Switching of Cancer-Associated Fibroblasts to Tumor Suppressive in Prostate Cancer DOI Creative Commons
Hongtao Song, Tong Lü, Donghui Han

et al.

Cancer Research, Journal Year: 2024, Volume and Issue: 84(22), P. 3728 - 3742

Published: Aug. 13, 2024

Prostate cancer rarely responds to immune-checkpoint blockade (ICB) therapies. Cancer-associated fibroblasts (CAF) are critical components of the immunologically "cold" tumor microenvironment and considered a promising target enhance immunotherapy response. In this study, we aimed reveal mechanisms regulating CAF plasticity identify potential strategies switch CAFs from protumorigenic antitumor phenotypes ICB efficacy in prostate cancer. Integration four single-cell RNA sequencing datasets defined CAFs, RNA-seq, flow cytometry, organoid model demonstrated functions two subtypes. Extracellular matrix-associated (ECM-CAF) promoted collagen deposition cell progression, lymphocyte-associated (Lym-CAF) exhibited an phenotype induced infiltration activation CD8+ T cells. YAP1 activity regulated ECM-CAF phenotype, silencing switching Lym-CAFs. NF-κB p65 was core transcription factor Lym-CAF subset, inhibited nuclear translocation p65. Selective depletion ECM-CAFs vivo T-cell enhanced therapeutic effects anti-PD-1 treatment on Overall, study revealed mechanism identity highlighted strategy for altering subtype suppress growth increase sensitivity ICB. Significance: regulates cancer-associated fibroblast can be targeted that promotes extracellular matrix tumor-suppressive stimulates immunity efficacy.

Language: Английский

Citations

11
Bispecific antibodies: advancing precision oncology DOI Creative Commons

M. Zurita Herrera,

G. Pretelli, Jayesh Desai

et al.

Trends in cancer, Journal Year: 2024, Volume and Issue: 10(10), P. 893 - 919

Published: Aug. 30, 2024

Bispecific antibodies (bsAbs) are engineered molecules designed to target two different epitopes or antigens. The mechanism of action is determined by the bsAb molecular targets and structure (or format), which can be manipulated create variable novel functionalities, including linking immune cells with tumor cells, dual signaling pathway blockade. Several bsAbs have already changed treatment landscape hematological malignancies select solid cancers. However, mechanisms resistance these agents understudied management toxicities remains challenging. Herein, we review principles in engineering, current understanding resistance, data for clinical application, provide a perspective on ongoing challenges future developments this field.

Language: Английский

Citations

11