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Genes Nov 2023The dendritic cell (DC) vaccine anti-cancer strategy involves tumour-associated antigen loading and maturation of autologous ex vivo cultured DCs, followed by infusion... (Review)
Review
The dendritic cell (DC) vaccine anti-cancer strategy involves tumour-associated antigen loading and maturation of autologous ex vivo cultured DCs, followed by infusion into the cancer patient. This strategy stemmed from the idea that to induce a robust anti-tumour immune response, it was necessary to bypass the fundamental immunosuppressive mechanisms of the tumour microenvironment that dampen down endogenous innate immune cell activation and enable tumours to evade immune attack. Even though the feasibility and safety of DC vaccines have long been confirmed, clinical response rates remain disappointing. Hence, the full potential of DC vaccines has yet to be reached. Whether this cellular-based vaccination approach will fully realise its position in the immunotherapy arsenal is yet to be determined. Attempts to increase DC vaccine immunogenicity will depend on increasing our understanding of DC biology and the signalling pathways involved in antigen uptake, maturation, migration, and T lymphocyte priming to identify amenable molecular targets to improve DC vaccine performance. This review evaluates various genetic engineering strategies that have been employed to optimise and boost the efficacy of DC vaccines.
Topics: Humans; Vaccine Efficacy; T-Lymphocytes; Neoplasms; Dendritic Cells; Vaccines; Tumor Microenvironment
PubMed: 38136940
DOI: 10.3390/genes14122118 -
Immunological Reviews Jan 2024Dendritic cells (DCs) are myeloid cells bridging the innate and adaptive immune system. By cross-presenting tumor-associated antigens (TAAs) liberated upon spontaneous... (Review)
Review
Dendritic cells (DCs) are myeloid cells bridging the innate and adaptive immune system. By cross-presenting tumor-associated antigens (TAAs) liberated upon spontaneous or therapy-induced tumor cell death to T cells, DCs occupy a pivotal position in the cancer immunity cycle. Over the last decades, the mechanisms linking cancer cell death to DC maturation, have been the focus of intense research. Growing evidence supports the concept that the mere transfer of TAAs during the process of cell death is insufficient to drive immunogenic DC maturation unless this process is coupled with the release of immunomodulatory signals by dying cancer cells. Malignant cells succumbing to a regulated cell death variant called immunogenic cell death (ICD), foster a proficient interface with DCs, enabling their immunogenic maturation and engagement of adaptive immunity against cancer. This property relies on the ability of ICD to exhibit pathogen-mimicry hallmarks and orchestrate the emission of a spectrum of constitutively present or de novo-induced danger signals, collectively known as damage-associated molecular patterns (DAMPs). In this review, we discuss how DCs perceive and decode danger signals emanating from malignant cells undergoing ICD and provide an outlook of the major signaling and functional consequences of this interaction for DCs and antitumor immunity.
Topics: Humans; Immunogenic Cell Death; Dendritic Cells; Cell Death; Neoplasms; Antigens, Neoplasm; Adaptive Immunity
PubMed: 38093416
DOI: 10.1111/imr.13301 -
ELife Aug 2023Cancer immunotherapies, in particular checkpoint blockade immunotherapy (CBT), can induce control of cancer growth, with a fraction of patients experiencing durable...
Cancer immunotherapies, in particular checkpoint blockade immunotherapy (CBT), can induce control of cancer growth, with a fraction of patients experiencing durable responses. However, the majority of patients currently do not respond to CBT and the molecular determinants of resistance have not been fully elucidated. Mounting clinical evidence suggests that the clonal status of neoantigens (NeoAg) impacts the anti-tumor T cell response. High intratumor heterogeneity (ITH), where the majority of NeoAgs are expressed subclonally, is correlated with poor clinical response to CBT and poor infiltration with tumor-reactive T cells. However, the mechanism by which ITH blunts tumor-reactive T cells is unclear. We developed a transplantable murine lung cancer model to characterize the immune response against a defined set of NeoAgs expressed either clonally or subclonally to model low or high ITH, respectively. Here we show that clonal expression of a weakly immunogenic NeoAg with a relatively strong NeoAg increased the immunogenicity of tumors with low but not high ITH. Mechanistically we determined that clonal NeoAg expression allowed cross-presenting dendritic cells to acquire and present both NeoAgs. Dual NeoAg presentation by dendritic cells was associated with a more mature DC phenotype and a higher stimulatory capacity. These data suggest that clonal NeoAg expression can induce more potent anti-tumor responses due to more stimulatory dendritic cell:T cell interactions. Therapeutic vaccination targeting subclonally expressed NeoAgs could be used to boost anti-tumor T cell responses.
Topics: Animals; Mice; Cross-Priming; Antigens, Neoplasm; Lung Neoplasms; T-Lymphocytes; Dendritic Cells
PubMed: 37548358
DOI: 10.7554/eLife.85263 -
Frontiers in Immunology 2023
Topics: Humans; Immunologic Factors; Adjuvants, Immunologic; Phenotype; Dendritic Cells
PubMed: 38193089
DOI: 10.3389/fimmu.2023.1353765 -
Biology Direct Nov 2023Cancer immunotherapy, alone or in combination with conventional therapies, has revolutionized the landscape of antineoplastic treatments, with dendritic cells (DC)... (Review)
Review
Cancer immunotherapy, alone or in combination with conventional therapies, has revolutionized the landscape of antineoplastic treatments, with dendritic cells (DC) emerging as key orchestrators of anti-tumor immune responses. Among the distinct DC subsets, conventional type 1 dendritic cells (cDC1) have gained prominence due to their unique ability to cross-present antigens and activate cytotoxic T lymphocytes. This review summarizes the distinctive characteristics of cDC1, their pivotal role in anticancer immunity, and the potential applications of cDC1-based strategies in immunotherapy.
Topics: Humans; Dendritic Cells; Neoplasms; Immunotherapy; CD8-Positive T-Lymphocytes
PubMed: 37907944
DOI: 10.1186/s13062-023-00430-5 -
Biomaterials Nov 2023Cancer vaccine holds vast promise in potentiating tumor immunotherapy. Here, we developed a simple cancer vaccine based on the liquid nitrogen-treated cells (LNT cells)...
Cancer vaccine holds vast promise in potentiating tumor immunotherapy. Here, we developed a simple cancer vaccine based on the liquid nitrogen-treated cells (LNT cells) that engineered by one-shot shocking of the live tumor cells in liquid nitrogen. In this vaccine, the obtained LNT cells served as both tumor antigens and delivery vehicles to load the adjuvant imiquimod (R837). This design could achieve efficient co-uptake of antigen/adjuvant by antigen presenting cells (APCs) and prolong in vivo retention of tumor antigens and adjuvants. This adjuvant-loaded LNT cells augmented in vivo antitumor responses and enhanced survival in melanoma-bearing mouse model compared with conventional whole-cell vaccine of the mixture of tumor lysis and adjuvant.
Topics: Mice; Animals; Cancer Vaccines; Adjuvants, Immunologic; Immunotherapy; Antigens, Neoplasm; Melanoma; Vaccination; Nitrogen; Dendritic Cells
PubMed: 37741150
DOI: 10.1016/j.biomaterials.2023.122319 -
Haematologica Jan 2024Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that presents with characteristic dark purple skin papules, plaques, and tumors,... (Review)
Review
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that presents with characteristic dark purple skin papules, plaques, and tumors, but may also involve the bone marrow, blood, lymph nodes, and central nervous system. The disease, which commonly affects older men but can also present in children, is associated with a distinct immunophenotype including universal expression of CD123, the α chain of the interleukin 3 receptor. Recently, tagraxofusp, a CD123-targeting drug consisting of the ligand for CD123, interleukin 3, conjugated to a truncated diphtheria toxin payload was approved for treatment of BPDCN. This was the first agent specifically approved for BPDCN and the first CD123 targeted agent in oncology. Here, we review the development of tagraxofusp, and the key preclinical insights and clinical data that led to approval. Tagraxofusp treatment is associated with a unique toxicity, capillary leak syndrome (CLS), which can be severe but is manageable with proper patient selection and monitoring, early recognition, and directed intervention. We outline our approach to the use of tagraxofusp and discuss open questions in the treatment of BPDCN. Overall, tagraxofusp represents a unique targeted therapy and a step forward in meeting an unmet need for patients with this rare disease.
Topics: Male; Child; Humans; Aged; Interleukin-3 Receptor alpha Subunit; Dendritic Cells; Hematologic Neoplasms; Recombinant Fusion Proteins; Acute Disease; Myeloproliferative Disorders; Skin Neoplasms
PubMed: 36951152
DOI: 10.3324/haematol.2022.282171 -
International Journal of Molecular... Feb 2024Atherosclerosis, a major contributor to cardiovascular morbidity and mortality, is characterized by chronic inflammation of the arterial wall. This inflammatory process... (Review)
Review
Atherosclerosis, a major contributor to cardiovascular morbidity and mortality, is characterized by chronic inflammation of the arterial wall. This inflammatory process is initiated and maintained by both innate and adaptive immunity. Dendritic cells (DCs), which are antigen-presenting cells, play a crucial role in the development of atherosclerosis and consist of various subtypes with distinct functional abilities. Following the recognition and binding of antigens, DCs become potent activators of cellular responses, bridging the innate and adaptive immune systems. The modulation of specific DC subpopulations can have either pro-atherogenic or atheroprotective effects, highlighting the dual pro-inflammatory or tolerogenic roles of DCs. In this work, we provide a comprehensive overview of the evolving roles of DCs and their subtypes in the promotion or limitation of atherosclerosis development. Additionally, we explore antigen pulsing and pharmacological approaches to modulate the function of DCs in the context of atherosclerosis.
Topics: Humans; Dendritic Cells; Atherosclerosis; Adaptive Immunity; Inflammation
PubMed: 38397127
DOI: 10.3390/ijms25042450 -
Current Treatment Options in Oncology Dec 2023The primary objective of this study is to evaluate the effectiveness of cancer vaccines containing genetically modified dendritic cells (DCs) in inducing... (Review)
Review
The primary objective of this study is to evaluate the effectiveness of cancer vaccines containing genetically modified dendritic cells (DCs) in inducing transformational immune responses. This paper sheds considerable light on DCs' function in advancing treatment techniques. This objective is achieved by thoroughly analyzing the many facets of DCs and their strategic integration into cancer treatment. Due to their role as immune response regulators, DCs can potentially enhance cancer treatment strategies. DCs have the potential to revolutionize immunotherapy, as shown by a comprehensive analysis of their numerous characteristics. The review deftly transitions from examining the fundamentals of preclinical research to delving into the complexities of clinical implementation while acknowledging the inherent challenges in translating DC vaccine concepts into tangible progress. The analysis also emphasizes the potential synergistic outcomes that can be achieved by combining DC vaccines with established pharmaceuticals, thereby emphasizing the importance of employing a holistic approach to enhance treatment efficacy. Despite the existence of transformative opportunities, advancement is hindered by several obstacles. The exhaustive analysis of technical complexities, regulatory dynamics, and upcoming challenges provides valuable insights for overcoming obstacles requiring strategic navigation to incorporate DC vaccines successfully. This document provides a comprehensive analysis of the developments in DC-based immunotherapy, concentrating on its potential to transform cancer therapy radically.
Topics: Humans; Immunotherapy; Dendritic Cells; Cancer Vaccines; Neoplasms
PubMed: 37962824
DOI: 10.1007/s11864-023-01143-7 -
Gut Microbes Dec 2023Aging is an inevitable natural process that impacts every individual, and understanding its effect on the gut microbiome and dendritic cell (DC) functionality in elderly... (Review)
Review
Aging is an inevitable natural process that impacts every individual, and understanding its effect on the gut microbiome and dendritic cell (DC) functionality in elderly subjects is crucial. DCs are vital antigen-presenting cells (APCs) that orchestrate the immune response, maintaining immune tolerance to self-antigens and bridging innate and adaptive immunity. With aging, there is a shift toward nonspecific innate immunity, resulting in a decline in adaptive immune responses. This alteration raises significant concerns about managing the health of an elderly population. However, the precise impact of aging and microbiome changes on DC function and their implications in lung-associated diseases remain relatively understudied. To illuminate this subject, we will discuss recent advancements in understanding the connections between aging, gut dysbiosis, DCs, and lung diseases. Emphasizing the key concepts linking age-related gut microbiome changes and DC functions, we will focus on their relevance to overall health and immune response in elderly individuals. This article aims to improve our understanding of the intricate relationship between aging, gut microbiome, and DCs, potentially benefiting the management of age-associated diseases and promoting healthy aging.
Topics: Aged; Humans; Dysbiosis; Gastrointestinal Microbiome; Immunity, Innate; Lung Diseases; Dendritic Cells
PubMed: 38087439
DOI: 10.1080/19490976.2023.2290643