The foundations of immune checkpoint blockade and the ipilimumab approval decennial

Nature Reviews Drug Discovery, Год журнала: 2021, Номер 21(7), С. 509 - 528

Опубликована: Дек. 22, 2021

Язык: Английский

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Resistance Mechanisms of Anti-PD1/PDL1 Therapy in Solid Tumors

Frontiers in Cell and Developmental Biology, Год журнала: 2020, Номер 8

Опубликована: Июль 21, 2020

In cancer-immunity cycle, the immune checkpoint PD1 and its ligand PDL1 act as accomplices to help tumors resist immunity-induced apoptosis promote tumor progression. Immunotherapy targeting PD1/PDL1 axis can effectively block pro-tumor activity. Anti-PD1/PDL1 therapy has achieved great success in past decade. However, only a subset of patients showed clinical responses. Most not benefit from anti-PD1/PDL1 therapy. Furthermore, large group responders would develop acquired resistance after initial Therefore, understanding mechanisms is necessary for improving efficacy. Currently, researchers have identified primary which include insufficient immunogenicity, disfunction MHCs, irreversible T cell exhaustion, IFN-γ signaling immunosuppressive microenvironment. Some oncogenic pathways also contribute resistance. Under pressure applied by therapy, experience immunoediting preserve beneficial mutations, upregulate compensatory inhibitory induce re-exhaustion cells, all may attenuate durability Here we explore underlying detail, review biomarkers that identifying among discuss strategies relieve

Язык: Английский

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Immunosenescence: a key player in cancer development

Journal of Hematology & Oncology, Год журнала: 2020, Номер 13(1)

Опубликована: Ноя. 10, 2020

Immunosenescence is a process of immune dysfunction that occurs with age and includes remodeling lymphoid organs, leading to changes in the function elderly, which closely related development infections, autoimmune diseases, malignant tumors. T cell-output decline an important feature immunosenescence as well production senescence-associated secretory phenotype, increased glycolysis, reactive oxygen species. Senescent cells exhibit abnormal phenotypes, including downregulation CD27, CD28, upregulation CD57, killer cell lectin-like receptor subfamily G, Tim-3, Tight, cytotoxic T-lymphocyte-associated protein 4, are tightly The role tumors sophisticated: many factors involved include cAMP, glucose competition, oncogenic stress tumor microenvironment, can induce senescence cells, macrophages, natural dendritic cells. Accordingly, these senescent could also affect progression. In addition, effect on response checkpoint blocking antibody therapy so far ambiguous due low participation elderly cancer patients clinical trials. Furthermore, other senescence-related interventions be possible genetic pharmacological methods, mTOR inhibition, interleukin-7 recombination, NAD+ activation. Overall, this review aims highlight characteristics its impact immunotherapy, especially future directions treatment through senescence-focused strategies.

Язык: Английский

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Biomarkers of aging

Science China Life Sciences, Год журнала: 2023, Номер 66(5), С. 893 - 1066

Опубликована: Апрель 11, 2023

Язык: Английский

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Antitumor activity without on-target off-tumor toxicity of GD2–chimeric antigen receptor T cells in patients with neuroblastoma

Science Translational Medicine, Год журнала: 2020, Номер 12(571)

Опубликована: Ноя. 25, 2020

Patients with neuroblastoma infused GD2-directed CAR-T cells experienced immune activation and transient tumor regressions without neurotoxicity.

Язык: Английский

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The association between albumin levels and survival in patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis

Frontiers in Molecular Biosciences, Год журнала: 2022, Номер 9

Опубликована: Дек. 2, 2022

Background: The albumin levels may potentially be used as a prognostic biomarker in patients with cancertreated immune checkpoint inhibitors (ICIs) due to its close relationship nutritional and inflammatory status. However, the available data is limited heterogeneous patient cohorts, sample sizes variable cut-offs. Therefore, we conducted systematic review meta-analysis evaluate association between survival outcomes treated ICIs. Methods: We using PubMed, Web of Science, Embase databases filter published studies up 1 June 2022. meta-analyses were performed generic inverse-variance method random-effects model high degree heterogeneity. primary outcome measure was hazard ratio (HR) 95% confidence intervals (CI). study protocol registered PROSPERO registry (Registration Number: CRD42022337746). Results: Thirty-six encompassing 8406 cancer advanced disease included meta-analyses. Almost half NSCLC cohorts (n = 15), 3.5 gr/dL most frequently cut-off 20). Patients lower had significantly increased risk death (HR: 1.65, CI: 1.52–1.80, p < 0.0001) than higher levels. Subgroup analyses for location, size, tumor type demonstrated consistent results. Furthermore, subgroup analysis eight continuous factor, every decrease associated by factor 10% 1.10, 1.05–1.16, 0.0002). Similar overall survival, an progression or compared 1.76, 1.40–2.21, 0.001). Conclusion: evidence demonstrates that Further research needed delineate role ICIs adjuvant setting, well possible benefit therapeutic approaches improve hypoalbuminemia.

Язык: Английский

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Manganese-phenolic nanoadjuvant combines sonodynamic therapy with cGAS-STING activation for enhanced cancer immunotherapy

Nano Today, Год журнала: 2022, Номер 43, С. 101405 - 101405

Опубликована: Янв. 25, 2022

Язык: Английский

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Targeting memory T cell metabolism to improve immunity

Journal of Clinical Investigation, Год журнала: 2022, Номер 132(1)

Опубликована: Янв. 3, 2022

Vaccination affords protection from disease by activating pathogen-specific immune cells and facilitating the development of persistent immunologic memory toward vaccine-specific pathogen. Current vaccine regimens are often based on efficiency acute response, not necessarily generation cells, in part because mechanisms underlying efficient remain incompletely understood. This Review describes recent advances defining T cell metabolism how these might be altered patients affected mitochondrial diseases or metabolic syndrome, who show higher susceptibility to recurrent infections rates failure. It discusses this new understanding could add way we think about memory, development, cancer immunotherapy.

Язык: Английский

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Gold Nanoparticles: Construction for Drug Delivery and Application in Cancer Immunotherapy

Pharmaceutics, Год журнала: 2023, Номер 15(7), С. 1868 - 1868

Опубликована: Июль 2, 2023

Cancer immunotherapy is an innovative treatment strategy to enhance the ability of immune system recognize and eliminate cancer cells. However, dose limitations, low response rates, adverse events pose significant challenges. To address these gold nanoparticles (AuNPs) have been explored as immunotherapeutic drug carriers owing their stability, surface versatility, excellent optical properties. This review provides overview advanced synthesis routes for AuNPs utilization improve precision therapies. The also emphasises various aspects AuNP-based immunotherapy, including loading, targeting strategies, release mechanisms. application combined with therapeutic efficacy are briefly discussed. Overall, we aimed provide a recent understanding advances, challenges, prospects anticancer applications.

Язык: Английский

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Dual Relationship Between Stromal Cells and Immune Cells in the Tumor Microenvironment

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Апрель 6, 2022

The tumor microenvironment (TME) plays a critical role in tumorigenesis and is comprised of different components, including cells, stromal immune cells. Among them, the relationship between each mediator involved construction TME can be understood by focusing on secreting or expressing factors from Therefore, understanding various interactions cellular component necessary for precise therapeutic approaches. In carcinoma, cells are well known to influence extracellular matrix (ECM) formation progression through multiple mediators. Immune respond causing cytotoxicity inflammatory responses. However, they escape immunoregulatory mechanisms. general, anti-cancer therapy has mainly been focused cancer themselves specific cell components. directly indirectly other partners, members such as also participate organization their mutual communication. this review, we summarized discussed positive negative relationships point view development use research applications strategies.

Язык: Английский

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