Cancer vaccines as promising immuno-therapeutics: platforms and current progress

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: March 18, 2022

Abstract Research on tumor immunotherapy has made tremendous progress in the past decades, with numerous studies entering clinical evaluation. The cancer vaccine is considered a promising therapeutic strategy of solid tumors. Cancer stimulates anti-tumor immunity antigens, which could be delivered form whole cells, peptides, nucleic acids, etc . Ideal vaccines overcome immune suppression tumors and induce both humoral cellular immunity. In this review, we introduced working mechanism summarized four platforms for development. We also highlighted research vaccines, especially focusing their application efficacy, might hopefully facilitate future design vaccine.

Language: Английский

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Immunosuppressive cells in cancer: mechanisms and potential therapeutic targets

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: May 18, 2022

Abstract Immunotherapies like the adoptive transfer of gene-engineered T cells and immune checkpoint inhibitors are novel therapeutic modalities for advanced cancers. However, some patients refractory or resistant to these therapies, mechanisms underlying tumor resistance have not been fully elucidated. Immunosuppressive such as myeloid-derived suppressive cells, tumor-associated macrophages, neutrophils, regulatory (Tregs), dendritic critical factors correlated with resistance. In addition, cytokines secreted by immunosuppressive also mediate progression escape Thus, targeting related signals is promising therapy improve efficacy immunotherapies reverse even certain success in preclinical studies specific types cancer, large perspectives unknown therapies undesirable outcomes clinical patients. this review, we comprehensively summarized phenotype, function, potential targets microenvironment.

Language: Английский

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FoxP3+ T regulatory cells in cancer: Prognostic biomarkers and therapeutic targets

Cancer Letters, Journal Year: 2020, Volume and Issue: 490, P. 174 - 185

Published: July 25, 2020

T Regulatory cells (Tregs) can have both protective and pathological roles. They maintain immune homeostasis inhibit responses in various diseases, including cancer. Proportions of Tregs the peripheral blood some cancer patients increase by approximately two-fold, compared to those healthy individuals. contribute development progression suppressing effector cell functions, thereby compromising tumor killing promoting growth. Highly immunosuppressive express upregulated levels transcription factor, Forkhead box protein P3 (FoxP3). Elevated FoxP3+ within microenvironment (TME) showed a positive correlation with poor prognosis patients. Despite success immunotherapy, use checkpoint inhibitors, significant proportion show low response rates as result primary or acquired resistance against therapy. Some mechanisms which underlie therapy are associated Treg suppressive function. In this review, we describe contribution development/progression, Treg-mediated immunosuppression. We discuss prognostic significance different cancers their potential biomarkers. also therapeutic strategies target combination other types immunotherapies aiming overcome improve clinical outcomes Overall, understanding could help more effective targeted enhance

Language: Английский

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Mechanisms and Regulation of Cellular Senescence

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(23), P. 13173 - 13173

Published: Dec. 6, 2021

Cellular senescence entails a state of an essentially irreversible proliferative arrest in which cells remain metabolically active and secrete range pro-inflammatory proteolytic factors as part the senescence-associated secretory phenotype. There are different types senescent cells, can be induced response to many DNA damage signals. Senescent accumulate tissues organs where they have distinct physiological pathological functions. Despite this diversity, all must able survive nondividing while protecting themselves from positive feedback loops linked constant activation response. This capacity requires changes core cellular programs. Understanding how cell undergo extensive their transcriptional programs, metabolism, heterochromatin patterns, structures induce common is crucial preventing cancer development/progression improving health during aging. In review, we discuss continuously evolve after initial highlight unifying features that define state.

Language: Английский

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The role of cancer-derived microRNAs in cancer immune escape

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: March 28, 2020

Abstract During malignant transformation, accumulated somatic mutations endow cancer cells with increased invasiveness and immunogenicity. Under selective pressure, these highly immunogenic develop multiple strategies to evade immune attack. It has been well established that could downregulate the expression of major histocompatibility complex, acquire alterations in interferon pathway, upregulate activities checkpoint pathways. Besides, secret numerous cytokines, exosomes, microvesicles regulate functions abundances components tumor microenvironment including effector professional antigen presentation cells. As vital determinant post-transcriptional regulation, microRNAs (miRNAs) not only participate initiation progression but also anti-cancer response. For instance, some miRNAs affect surveillance escape by interfering attack-associated molecules. A growing body evidence indicated cancer-derived modulatory might be promising targets counteract escape. In this review, we summarized role discussed their potential clinical application as treatment targets.

Language: Английский

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Cancer immunotherapy resistance based on immune checkpoints inhibitors: Targets, biomarkers, and remedies

Drug Resistance Updates, Journal Year: 2020, Volume and Issue: 53, P. 100718 - 100718

Published: July 15, 2020

Cancer is one of the main public health problems in world. Systemic therapies such as chemotherapy and more recently target well immunotherapy have improved prognosis this large group complex malignant diseases. However, frequent emergence multidrug resistance (MDR) mechanisms major impediments towards curative treatment cancer. While several drug chemoresistance are defined, to still insufficiently unclear due complexity immune response its dependence on host. Expression regulation checkpoint molecules (such PD-1, CD279; PD-L1, CD274; CTLA-4, CD152) play a key role immunotherapy. In regard, based checkpoints inhibitors (ICIs) common clinical approach for patients with poor when other first-line failed. Unfortunately, about 70 % classified non-responders, or they progress after initial these ICIs. Multiple factors can be related resistance: characteristics tumor microenvironment (TME); presence infiltrating lymphocytes (TILs), CD8 + T cells associated treatment-response; macrophages (TAMs); activation certain regulators (like PIK3γ PAX4) found present non-responders; low percentage PD-L1 expressing cells; mutational burden (TMB); gain loss antigen-presenting molecules; genetic epigenetic alterations correlated resistance. This review provides an update current state presenting targets, biomarkers remedies overcome

Language: Английский

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Adaptive Mechanisms of Tumor Therapy Resistance Driven by Tumor Microenvironment

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: March 1, 2021

Cancer is a disease which frequently has poor prognosis. Although multiple therapeutic strategies have been developed for various cancers, including chemotherapy, radiotherapy, and immunotherapy, resistance to these treatments impedes the clinical outcomes. Besides active driven by genetic epigenetic alterations in tumor cells, microenvironment (TME) also reported be crucial regulator tumorigenesis, progression, resistance. Here, we propose that adaptive mechanisms of are closely connected with TME rather than depending on non-cell-autonomous changes response treatment. comprehensive understanding need further investigation fully elucidate resistance, many targeting successful. In this review, report recent advances concerning molecular events important factors involved TME, particularly focusing contributions provide insights into potential methods or translational medicine overcome therapy

Language: Английский

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Metal-Phenolic Network-Enabled Lactic Acid Consumption Reverses Immunosuppressive Tumor Microenvironment for Sonodynamic Therapy

ACS Nano, Journal Year: 2021, Volume and Issue: 15(10), P. 16934 - 16945

Published: Oct. 18, 2021

Nanomedicine has revolutionized cancer therapeutic strategies but not completely changed the outcomes of tricky tumors that evolve a sophisticated immunosuppressive tumor microenvironment (TME) such as acidification. Here, metal-phenolic network-based nanocomplex embedded with lactate oxidase (LOX) and mitochondrial respiration inhibitor atovaquone (ATO) was constructed for TME remodeling sonodynamic therapy (SDT). In this nanocomplex, sonosensitizer chlorin e6-conjugated polyphenol derivative can induce generation lethal reactive oxygen species upon ultrasound irradiation. LOX served catalyst intracellular lactic acid exhaustion, ATO led to dysfunction decrease consumption. This reversed status by alleviating hypoxia acidic TME, achieving characteristic enhancement SDT inhibition proliferation metastasis.

Language: Английский

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Lung fibroblasts facilitate pre-metastatic niche formation by remodeling the local immune microenvironment

Immunity, Journal Year: 2022, Volume and Issue: 55(8), P. 1483 - 1500.e9

Published: July 30, 2022

Language: Английский

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Understanding and targeting resistance mechanisms in cancer

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 22, 2023

Resistance to cancer therapies has been a commonly observed phenomenon in clinical practice, which is one of the major causes treatment failure and poor patient survival. The reduced responsiveness cells multifaceted that can arise from genetic, epigenetic, microenvironmental factors. Various mechanisms have discovered extensively studied, including drug inactivation, intracellular accumulation by uptake or increased efflux, target alteration, activation compensatory pathways for cell survival, regulation DNA repair death, tumor plasticity, microenvironments (TMEs). To overcome resistance, variety strategies proposed, are designed enhance effectiveness reduce resistance. These include identifying biomarkers predict response new targets, developing targeted drugs, combination targeting multiple signaling pathways, modulating TME. present article focuses on different resistance corresponding tackling approaches with recent updates. Perspectives polytherapy mechanisms, novel nanoparticle delivery systems, advanced design tools overcoming also reviewed.

Language: Английский

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