Visualizing Synaptic Transfer of Tumor Antigens among Dendritic Cells

Ruhland, Megan K.; Roberts, Ed; Cai, En; Mujal, Adriana M.; Marchuk, Kyle; Beppler, Casey; Nam, David; Serwas, Nina K.; Binnewies, Mikhail; Krummel, Matthew F.

doi:10.1016/j.ccell.2020.05.002

Cited by 157 publications

(127 citation statements)

References 47 publications

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“…During an effective antitumor immune response, APCs uptake and present tumor antigens to T cells, leading to T cell activation for tumor destruction 45 . In an established tumor microenvironment, majority of the infiltrating T cells are dysfunctional 46 .…”

Section: Discussionmentioning

confidence: 99%

PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade

et al. 2020

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Immune checkpoint blockade therapies have shown clinical promise in a variety of cancers, but how tumor-infiltrating T cells are activated remains unclear. In this study, we explore the functions of PD-L1 on dendritic cells (DCs), which highly express PD-L1. We observe that PD-L1 on DC plays a critical role in limiting T cell responses. Type 1 conventional DCs are essential for PD-L1 blockade and they upregulate PD-L1 upon antigen uptake. Upregulation of PD-L1 on DC is mediated by type II interferon. While DCs are the major antigen presenting cells for cross-presenting tumor antigens to T cells, subsequent PD-L1 upregulation protects them from killing by cytotoxic T lymphocytes, yet dampens the antitumor responses. Blocking PD-L1 in established tumors promotes re-activation of tumor-infiltrating T cells for tumor control. Our study identifies a critical and dynamic role of PD-L1 on DC, which needs to be harnessed for better invigoration of antitumor immune responses.

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Section: Discussionmentioning

confidence: 99%

PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade

et al. 2020

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“…Although recent findings have indicated that there is a synapse between various DCs to share tumor antigens ( 107 ), human DCs can be divided into plasmacytoid DC (pDC), conventional DC (cDC), and monocyte-derived DCs (MoDC) subsets. The cDCs can also be subdivided into cDC1 and cDC2 subgroups ( 108 – 110 ).…”

Section: Dcs In the Tumor Microenvironment And Dc-based Vaccine Develmentioning

confidence: 99%

From Melanoma Development to RNA-Modified Dendritic Cell Vaccines: Highlighting the Lessons From the Past

et al. 2021

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Although melanoma remains the deadliest skin cancer, the current treatment has not resulted in the desired outcomes. Unlike chemotherapy, immunotherapy has provided more tolerable approaches and revolutionized cancer therapy. Although dendritic cell-based vaccines have minor side effects, the undesirable response rates of traditional approaches have posed questions about their clinical translation. The immunosuppressive tumor microenvironment can be the underlying reason for their low response rates. Immune checkpoints and indoleamine 2,3-dioxygenase have been implicated in the induction of immunosuppressive tumor microenvironment. Growing evidence indicates that the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/Protein kinase B (PKB) (PI3K/AKT) pathways, as the main oncogenic pathways of melanoma, can upregulate the tumoral immune checkpoints, like programmed death-ligand 1. This study briefly represents the main oncogenic pathways of melanoma and highlights the cross-talk between these oncogenic pathways with indoleamine 2,3-dioxygenase, tumoral immune checkpoints, and myeloid-derived suppressor cells. Moreover, this study sheds light on a novel tumor antigen on melanoma, which has substantial roles in tumoral immune checkpoints expression, indoleamine 2,3-dioxygenase secretion, and stimulating the oncogenic pathways. Finally, this review collects the lessons from the previous unsuccessful trials and integrates their lessons with new approaches in RNA-modified dendritic cell vaccines. Unlike traditional approaches, the advances in single-cell RNA-sequencing techniques and RNA-modified dendritic cell vaccines along with combined therapy of the immune checkpoint inhibitors, indoleamine 2,3-dioxygenase inhibitor, and RNA-modified dendritic cell-based vaccine can overcome these auto-inductive loops and pave the way for developing robust dendritic cell-based vaccines with the most favorable response rate and the least side effects.

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“…DCs are the most efficient antigen-presenting cells that take up, process and present antigens to T cells, which contribute to the initiation and progression of immune responses 20 . Early studies reported that DC-derived EVs expressed high levels of functional major histocompatibility complex (MHC) class I (MHC-I) and class II (MHC-II), MHC-peptide complexes, T cell costimulatory molecules, and tumor antigens 21 - 23 . In addition, it was shown that EVs derived from LPS-induced DCs carried multiple classes of RNAs, including miRNAs, small nucleolar RNAs, Y-RNAs, tRNAs, and small nuclear RNAs 24 , which may have roles in balancing T helper 1(Th1)/Th2 responses 25 .…”

Section: Characteristics and Functions Of Evs From Cells Associated Wmentioning

confidence: 99%

Extracellular vesicles in Inflammatory Skin Disorders: from Pathophysiology to Treatment

Shao¹,

Fang²,

Li³

et al. 2020

Theranostics

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Extracellular vesicles (EVs), naturally secreted by almost all known cell types into extracellular space, can transfer their bioactive cargos of nucleic acids and proteins to recipient cells, mediating cell-cell communication. Thus, they participate in many pathogenic processes including immune regulation, cell proliferation and differentiation, cell death, angiogenesis, among others. Cumulative evidence has shown the important regulatory effects of EVs on the initiation and progression of inflammation, autoimmunity, and cancer. In dermatology, recent studies indicate that EVs play key immunomodulatory roles in inflammatory skin disorders, including psoriasis, atopic dermatitis, lichen planus, bullous pemphigoid, systemic lupus erythematosus, and wound healing. Importantly, EVs can be used as biomarkers of pathophysiological states and/or therapeutic agents, both as carriers of drugs or even as a drug by themselves. In this review, we will summarize current research advances of EVs from different cells and their implications in inflammatory skin disorders, and further discuss their future applications, updated techniques, and challenges in clinical translational medicine.

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Visualizing Synaptic Transfer of Tumor Antigens among Dendritic Cells

Cited by 157 publications

References 47 publications

PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade

PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade

From Melanoma Development to RNA-Modified Dendritic Cell Vaccines: Highlighting the Lessons From the Past

Extracellular vesicles in Inflammatory Skin Disorders: from Pathophysiology to Treatment

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