Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Апрель 2, 2024

Abstract Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, immune cells, plays a crucial role response modulation. Nanoparticles, engineered to reshape TME, shown promising results enhancing by facilitating targeted These nanoparticles can suppress fibroblast activation, promote M1 macrophage polarization, aid dendritic cell maturation, encourage T infiltration. Biomimetic further enhance increasing internalization agents cells such as cells. Moreover, exosomes, whether naturally secreted body or bioengineered, been explored regulate TME immune-related affect cancer immunotherapy. Stimuli-responsive nanocarriers, activated pH, redox, light conditions, exhibit potential accelerate co-application with checkpoint inhibitors is an emerging strategy boost anti-tumor immunity. With their ability induce long-term immunity, nanoarchitectures are structures development. This review underscores critical overcoming current driving advancement modification.

Язык: Английский

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Nanomedicine Strategies in Conquering and Utilizing the Cancer Hypoxia Environment

ACS Nano, Год журнала: 2023, Номер 17(21), С. 20875 - 20924

Опубликована: Окт. 23, 2023

Cancer with a complex pathological process is major disease to human welfare. Due the imbalance between oxygen (O2) supply and consumption, hypoxia natural characteristic of most solid tumors an important obstacle for cancer therapy, which closely related tumor proliferation, metastasis, invasion. Various strategies exploit feature have been developed in past decade, can be used alleviate hypoxia, or utilize targeted delivery diagnostic imaging. The include delivering O2, situ O2 generation, reprogramming vascular system, decreasing inhibiting HIF-1 pathways. On other side, also utilized hypoxia-responsive chemical construction hypoxia-active prodrug-based strategies. Taking advantage region, number methods applied identify keep track changes hypoxia. Herein, we thoroughly review recent progress nanomedicine both conquering utilizing combat put forward prospect emerging nanomaterials future clinical transformation, hopes provide perspectives design.

Язык: Английский

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Autophagy-amplifying nanoparticles evoke immunogenic cell death combined with anti-PD-1/PD-L1 for residual tumors immunotherapy after RFA

Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)

Опубликована: Окт. 3, 2023

Incomplete radiofrequency ablation (IRFA) triggers mild protective autophagy in residual tumor cells and results an immunosuppressive microenvironment. This accelerates the recurrence of tumors causes resistance to anti-PD-1/PDL1 therapy, which bringing a great clinical challenge immunotherapy. Mild activation can promote cancer cell survival while further amplification contributes immunogenic death (ICD). To this regard, we constructed active targeting zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) loaded with STF62247 or both BMS202, namely STF62247@ZIF-8/PEG-FA (SZP) STF62247-BMS202@ZIF-8/PEG-FA (SBZP) NPs. We found that SZP NPs inhibited proliferation stimulated apoptosis exposed sublethal heat stress autophagy-dependent manner. Further discovered could amplify evoke their ICD, dramatically boosted maturation dendritic (DCs). Through vaccination experiments, for first time + treatment efficiently suppress growth new establish long-term immunological memory. Furthermore, SBZP remarkably ICD cells, obviously activate anti-tumor immune microenvironment, significantly inhibit tumors. Thus, amplified coupled therapy is potentially novel strategy treating after IRFA.

Язык: Английский

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Cellular heterogeneity in TNF/TNFR1 signalling: live cell imaging of cell fate decisions in single cells

Cell Death and Disease, Год журнала: 2024, Номер 15(3)

Опубликована: Март 11, 2024

Cellular responses to TNF are inherently heterogeneous within an isogenic cell population and across different types. promotes survival by activating pro-inflammatory NF-κB MAPK signalling pathways but may also trigger apoptosis necroptosis. Following stimulation, the fate of individual cells is governed balance pro-survival pro-apoptotic pathways. To elucidate molecular mechanisms driving heterogenous TNF, quantifying TNF/TNFR1 at single-cell level crucial. Fluorescence live-cell imaging techniques offer real-time, dynamic insights into processes in single cells, allowing for detection rapid transient changes, as well identification subpopulations, that likely be missed with traditional endpoint assays. Whilst fluorescence has been employed extensively investigate TNF-induced inflammation death, it underutilised studying role pathway crosstalk guiding cell-fate decisions cells. Here, we outline various opportunities during how these interactions govern TNF. We advocate use cell-to-cell variability Understanding overcoming cellular heterogeneity response modulators could lead development targeted therapies diseases associated aberrant signalling, such rheumatoid arthritis, metabolic syndrome, cancer.

Язык: Английский

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Emerging role of immunogenic cell death in cancer immunotherapy

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Май 10, 2024

Cancer immunotherapy, such as immune checkpoint blockade (ICB), has emerged a groundbreaking approach for effective cancer treatment. Despite its considerable potential, clinical studies have indicated that the current response rate to immunotherapy is suboptimal, primarily attributed low immunogenicity in certain types of malignant tumors. Immunogenic cell death (ICD) represents form regulated (RCD) capable enhancing tumor and activating tumor-specific innate adaptive responses immunocompetent hosts. Therefore, gaining deeper understanding ICD evolution crucial developing more therapeutic strategies. This review focuses exclusively on both historical recent discoveries related modes their mechanistic insights, particularly within context immunotherapy. Our findings are also highlighted, revealing mode induction facilitated by atypical interferon (IFN)-stimulated genes (ISGs), including polo-like kinase 2 ( PLK2 ), during hyperactive type I IFN signaling. The concludes discussing potential ICD, with special attention relevance preclinical settings field

Язык: Английский

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Targeting autophagy overcomes cancer‐intrinsic resistance to CAR‐T immunotherapy in B‐cell malignancies

Cancer Communications, Год журнала: 2024, Номер 44(3), С. 408 - 432

Опубликована: Фев. 26, 2024

Chimeric antigen receptor T (CAR-T) therapy has substantially revolutionized the clinical outcomes of patients with hematologic malignancies, but cancer-intrinsic mechanisms underlying resistance to CAR-T cells remain yet be fully understood. This study aims explore molecular determinants cancer cell sensitivity cell-mediated killing and provide a better understanding potential modulation improve efficacy.

Язык: Английский

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Lenvatinib resistance mechanism and potential ways to conquer

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Апрель 20, 2023

Graphical Abstract In this review, we summerized the absorption, distribution, metabolism, excretion of lenvatinib in clinic. The lastest mechanism and potential approches to overcome resistance caused by were supplied.

Язык: Английский

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Emerging dimensions of autophagy in melanoma

Autophagy, Год журнала: 2024, Номер 20(8), С. 1700 - 1711

Опубликована: Март 18, 2024

Macroautophagy/autophagy has previously been regarded as simply a way for cells to deal with nutrient emergency. But explosive work in the last 15 years given increasingly new knowledge our understanding of this process. Many functions autophagy that are unveiled from recent studies, however, cannot be reconciled conventional view cell survival but, instead, point being integrally involved at deeper level biology, playing critical role maintaining homeostasis and promoting an integrated stress/immune response. The appreciation evolutionary trajectory cancer interaction immune system provides mechanistic framework clinical benefits autophagy-based therapies. Here, we examine current mechanisms highly plastic aggressive melanoma model disease human malignancy, while highlighting emerging dimensions indicating is play beyond its classical face.

Язык: Английский

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Biomarker development for PD-(L)1 axis inhibition: a consensus view from the SITC Biomarkers Committee

Journal for ImmunoTherapy of Cancer, Год журнала: 2024, Номер 12(7), С. e009427 - e009427

Опубликована: Июль 1, 2024

Therapies targeting the programmed cell death protein-1/programmed death-ligand 1 (PD-L1) (abbreviated as PD-(L)1) axis are a significant advancement in treatment of many tumor types. However, patients receiving these agents fail to respond or have an initial response followed by cancer progression. For patients, while subsequent immunotherapies that either target different immune biology non-immune combination therapies reasonable options, lack predictive biomarkers follow-on is impeding progress field. This review summarizes current knowledge mechanisms driving resistance PD-(L)1 therapies, state biomarker development along this axis, and inherent challenges future for immunotherapies. Innovation application novel patient selection strategies required accelerate delivery effective treatments most likely respond.

Язык: Английский

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Exploiting Autophagy-Dependent Neoantigen Presentation in Tumor Microenvironment

Genes, Год журнала: 2023, Номер 14(2), С. 474 - 474

Опубликована: Фев. 13, 2023

Autophagy constitutes a well-known homeostatic and catabolic process that is responsible for degradation recycling of cellular components. It key regulatory mechanism several functions, whereas its dysregulation associated with tumorigenesis, tumor–stroma interactions resistance to cancer therapy. A growing body evidence has proven autophagy affects the tumor microenvironment, while it also considered factor function immune cells, such as APCs, T-cells, macrophages. Moreover, implicated in presentation neo-antigens cells both MHC-I MHC-II dendritic (DCs) functional activity by creating T-cell memory, well cross-presentation internalization process. Currently, crucial role immunotherapy. Emergence immunotherapy already shown some remarkable results, having changed therapeutic strategy clinical practice types. Despite these promising long-term responses, patients seem lack ability respond checkpoint inhibitors. Thus, through neo-antigen potential target order strengthen or attenuate effects against different types cancer. This review will shed light on recent advances future directions autophagy-dependent consequently malignant tumors.

Язык: Английский

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