Enhancing immunotherapy response in melanoma: myeloid-derived suppressor cells as a therapeutic target

Journal of Clinical Investigation, Год журнала: 2023, Номер 133(13)

Опубликована: Июль 2, 2023

Despite the remarkable success of immune checkpoint inhibitors (ICIs) in melanoma treatment, resistance to them remains a substantial clinical challenge. Myeloid-derived suppressor cells (MDSCs) represent heterogeneous population myeloid that can suppress antitumor responses mediated by T and natural killer promote tumor growth. They are major contributors ICI play crucial role creating an immunosuppressive microenvironment. Therefore, targeting MDSCs is considered promising strategy improve therapeutic efficacy ICIs. This Review describes mechanism MDSC-mediated suppression, preclinical studies on MDSC targeting, potential strategies for inhibiting functions immunotherapy.

Язык: Английский

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Elesclomol Loaded Copper Oxide Nanoplatform Triggers Cuproptosis to Enhance Antitumor Immunotherapy

Advanced Science, Год журнала: 2024, Номер 11(18)

Опубликована: Март 2, 2024

Abstract The induction of cuproptosis, a recently identified form copper‐dependent immunogenic cell death, is promising approach for antitumor therapy. However, sufficient accumulation intracellular copper ions (Cu 2+ ) in tumor cells essential inducing cuproptosis. Herein, an intelligent cuproptosis‐inducing nanosystem constructed by encapsulating oxide (CuO) nanoparticles with the ionophore elesclomol (ES). After uptake cells, ES@CuO degraded to release Cu and ES synergistically trigger thereby significantly inhibiting growth murine B16 melanoma cells. Moreover, further promoted cuproptosis‐mediated immune responses reprogrammed immunosuppressive microenvironment increasing number tumor‐infiltrating lymphocytes secreted inflammatory cytokines. Additionally, combining programmed death‐1 (PD‐1) immunotherapy substantially increased efficacy melanoma. Overall, findings this study can lead use novel strategy therapy, which may enhance checkpoint inhibitor

Язык: Английский

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Exosome camouflaged coordination-assembled Iridium(III) photosensitizers for apoptosis-autophagy-ferroptosis induced combination therapy against melanoma

Biomaterials, Год журнала: 2023, Номер 301, С. 122212 - 122212

Опубликована: Июнь 24, 2023

Язык: Английский

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Role of natural products in tumor therapy from basic research and clinical perspectives

Acta Materia Medica, Год журнала: 2024, Номер 3(2)

Опубликована: Янв. 1, 2024

Cancer is the leading cause of morbidity and mortality worldwide an important barrier to lengthening life expectancy in every country. Natural products are receiving increased attention from researchers globally increasing numbers natural approved for clinical studies involving cancer recent years. To gain more insight into that have undergone trials treatment, a comprehensive search was conducted. The https://clinicaltrials.gov website searched relevant product information up December 2022. terms included different types cancers, such as colorectal, lung, breast, gynecologic, kidney, bladder, melanoma, pancreatic, hepatocellular, gastric haematologic. Then, PubMed Web Science were articles February 2024. Hence, we listed existing about used treatment cancers discussed preclinical some promising their targets, indications, underlying mechanisms action. Our intent provide basic readers who interested or majoring obtain deeper understanding progress actions

Язык: Английский

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Tumor-Infiltrating Lymphocyte Therapy in Melanoma: Facts to the Future

Clinical Cancer Research, Год журнала: 2022, Номер 29(10), С. 1835 - 1854

Опубликована: Дек. 9, 2022

Abstract Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) is gaining momentum and demonstrating durable responses in patients advanced melanoma. Although increasingly considered as a treatment option for select melanoma, TIL not yet approved by any regulatory agency. Pioneering studies first-generation therapy, undertaken before the advent of modern melanoma therapeutics, demonstrated clinical efficacy remarkable long-term overall survival, reaching beyond 20 months responding patients. multistep process harvesting patient-specific tumor-resident T cells from tumors, ex vivo T-cell expansion, re-infusion into same patient after lymphodepleting preparative regimen, subsequent supportive IL2 administration. Objective response rates between 30% 50% have consistently been observed heavily pretreated metastatic including those who progressed immune checkpoint inhibitors BRAF targeted agents, population high unmet medical need. significant strides made refinement strategies to optimize selection, enhance production, improve are being explored. Here, we review past present experience, current challenges, practical considerations, future aspirations evolution well other solid tumors.

Язык: Английский

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Encapsulation of Platinum Prodrugs into PC7A Polymeric Nanoparticles Combined with Immune Checkpoint Inhibitors for Therapeutically Enhanced Multimodal Chemotherapy and Immunotherapy by Activation of the STING Pathway

Advanced Science, Год журнала: 2022, Номер 10(4)

Опубликована: Дек. 11, 2022

Abstract Tumor immunotherapy has emerged as one of the most promising therapeutic methods to treat cancer. Despite its clinical application, immunosuppressive tumor microenvironment compromises efficiency this technique. To overcome limitation, many research efforts have been devoted development agents that reprogram through novel mechanisms. Over last decade, compounds intervene immunogenic stimulator interferon genes (STING) pathway with potential for development. Herein, encapsulation chemotherapeutic platinum complexes a polymer cyclic seven‐membered ring (PC7A)‐based into pH‐responsive nanoparticles multimodal therapeutically enhanced chemotherapy and is presented. This study represents first nanomaterial dual activation mechanism STING DNA fragmentation well PC7A binding. The combination these immune checkpoint inhibitors demonstrates nearly fully eradicate colorectal inside mouse model by using pathway.

Язык: Английский

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Dissolvable Self‐Locking Microneedle Patches Integrated with Immunomodulators for Cancer Immunotherapy

Advanced Materials, Год журнала: 2022, Номер 35(10)

Опубликована: Дек. 18, 2022

Abstract Advancements in micro‐resolution 3D printers have significantly facilitated the development of highly complex mass‐producible drug delivery platforms. Conventionally, due to limitations micro‐milling machineries, dissolvable microneedles (MNs) are mainly fabricated cone‐shaped geometry with limited accuracy. Herein, overcome conventional MNs, a novel projection micro‐stereolithography printer‐based self‐locking MN for precise skin insertion, adhesion, and transcutaneous microdose is presented. The consists sharp skin‐penetrating tip, wide interlocking body, narrow base mechanical supports over flexible hydrocolloid patch improve accuracy penetration into irregular surfaces. Melanoma, type cancer, selected as model investigation MNs its uneven surface. In vivo immunotherapy efficacy evaluated by integrating SD‐208, transforming growth factor‐β (TGF‐β) inhibitor that suppresses proliferation metastasis tumors, anti‐PD‐L1 ( PD‐L1 Ab), an immune checkpoint induces T cell‐mediated tumor cell death, comparing them intratumoral injection. Evaluation Ab)/SD‐208 effectiveness B16F10 melanoma‐bearing mice confirms improved dose compared

Язык: Английский

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Phenotype Switching and the Melanoma Microenvironment; Impact on Immunotherapy and Drug Resistance

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(2), С. 1601 - 1601

Опубликована: Янв. 13, 2023

Melanoma, a highly heterogeneous tumor, is comprised of functionally diverse spectrum cell phenotypes and subpopulations, including stromal cells in the tumor microenvironment (TME). Melanoma has been shown to dynamically shift between different transcriptional states or phenotypes. This referred as phenotype switching melanoma, it involves quiescent proliferative cycle states, dramatic shifts invasiveness, well changes signaling pathways melanoma cells, immune composition TME. plasticity associated with altered gene expression cancer-associated fibroblasts, extracellular matrix, which drive metastatic cascade therapeutic resistance. Therefore, resistance therapy not only dependent on genetic evolution, but also suggested be driven by adaptive phenotypic plasticity. review discusses recent findings switching, immunotherapy resistance, balancing homeostatic TME subpopulations. We discuss future perspectives biology neural crest-like state(s) melanoma.

Язык: Английский

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SIRT7 orchestrates melanoma progression by simultaneously promoting cell survival and immune evasion via UPR activation

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Март 15, 2023

Abstract Melanoma is the most lethal type of skin cancer, originating from malignant transformation melanocyte. While development targeted therapy and immunotherapy has gained revolutionary advances in potentiating therapeutic effect, prognosis patients with melanoma still suboptimal. During tumor progression, frequently encounters stress both endogenous exogenous sources microenvironment. SIRT7 a nuclear-localized deacetylase which activity highly dependent on intracellular nicotinamide adenine dinucleotide (NAD + ), versatile biological functions maintaining cell homeostasis. Nevertheless, whether regulates biology immunology under stressful microenvironment remains elusive. Herein, we reported that orchestrates progression by simultaneously promoting survival immune evasion via activation unfolded protein response. We first identified expression was significantly increased one sirtuins family upon stress. Then, proved deficiency potentiated death vitro suppressed growth vivo. Mechanistically, selectively activated IRE1α-XBP1 axis to potentiate pro-survival ERK signal pathway secretion tumor-promoting cytokines. directly de-acetylated SMAD4 antagonize TGF-β-SMAD4 signal, relieved transcriptional repression IRE1α induced axis. Moreover, up-regulation eradicated anti-tumor immunity PD-L1 Additionally, synergized effect suppression anti-PD-1 checkpoint blockade also investigated. Taken together, can be employed as promising target restrain increase immunotherapy.

Язык: Английский

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The role of mitochondria in the resistance of melanoma to PD-1 inhibitors

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

Опубликована: Май 23, 2023

Abstract Malignant melanoma is one of the most common tumours and has highest mortality rate all types skin cancers worldwide. Traditional novel therapeutic approaches, including surgery, targeted therapy immunotherapy, have shown good efficacy in treatment melanoma. At present, mainstay for immunotherapy combined with other strategies. However, immune checkpoint inhibitors, such as PD-1 are not particularly effective clinical patients Changes mitochondrial function may affect development inhibitors. To elucidate role mitochondria resistance to this review comprehensively summarises occurrence melanoma, targets related cells changes different resistant This help develop strategies improving response inhibitors prolonging survival by activating tumour T cells.

Язык: Английский

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