Targeting the Immunoregulator SRA/CD204 Potentiates Specific Dendritic Cell Vaccine-Induced T-cell Response and Antitumor Immunity

Yi, Huanfa; Guo, Chunqing; Yu, Xiaofei; Gao, Ping; Qian, Jie; Zuo, Daming; Manjili, Masoud H.; Fisher, Paul B.; Subjeck, John R.; Wang, Xiangyang

doi:10.1158/0008-5472.can-11-1801

Cited by 50 publications

(53 citation statements)

References 34 publications

(46 reference statements)

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“…For instance, nanoparticle-Ag complexes are efficiently taken up by DCs (49). Downregulation of SRA/CD204, a pattern recognition scavenger receptor, strongly enhances DC-mediated antitumor immunity (50). We have shown that increased AZI2 expression in GMDCs significantly enhanced the efficacy to activate CD4 + T cells in vivo.…”

Section: Discussionmentioning

confidence: 85%

Critical Role of AZI2 in GM-CSF–Induced Dendritic Cell Differentiation

Fukasaka

Ori

Kawagoe

et al. 2013

The Journal of Immunology

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TNFR-associated factor family member–associated NF-κB activator (TANK)–binding kinase 1 (TBK1) is critical for the activation of IFN regulatory factor 3 and type I IFN production upon virus infection. A set of TBK1-binding proteins, 5-azacytidine–induced gene 2 (AZI2; also known as NAP1), TANK, and TBK1-binding protein 1 (TBKBP1), have also been implicated in the production of type I IFNs. Among them, TANK was found to be dispensable for the responses against virus infection. However, physiological roles of AZI2 and TBKBP1 have yet to be clarified. In this study, we found that none of these TBK1-binding proteins is critical for type I IFN production in mice. In contrast, AZI2, but not TBKBP1, is critical for the differentiation of conventional dendritic cells (cDCs) from bone marrow cells in response to GM-CSF. AZI2 controls GM-CSF–induced cell cycling of bone marrow cells via TBK1. GM-CSF–derived DCs from AZI2-deficient mice show severe defects in cytokine production and T cell activation both in vitro and in vivo. Reciprocally, overexpression of AZI2 results in efficient generation of cDCs, and the cells show enhanced T cell activation in response to Ag stimulation. Taken together, AZI2 expression is critical for the generation of cDCs by GM-CSF and can potentially be used to increase the efficiency of immunization by cDCs.

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Section: Discussionmentioning

confidence: 85%

Critical Role of AZI2 in GM-CSF–Induced Dendritic Cell Differentiation

Fukasaka

Ori

Kawagoe

et al. 2013

The Journal of Immunology

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“…Our proof-of-principle studies demonstrate that downregulation of SRA in DCs enhances the immunostimulatory activity of a DC vaccine (157). We show that SRA-silenced DCs carrying melanoma antigen gp100 are more efficient than controls in mobilizing antigen-specific CTLs, leading to improved control of established melanoma and its metastases.…”

Section: Hsp110 and Grp170-binding Receptors And Vaccine Designmentioning

confidence: 84%

“…We show that SRA-silenced DCs carrying melanoma antigen gp100 are more efficient than controls in mobilizing antigen-specific CTLs, leading to improved control of established melanoma and its metastases. This enhanced antitumor efficacy correlates positively with greater tumor-infiltrating CD8 + T cells and NK cells, as well as increased intratumoral ratios of effector T cells to regulatory T cells (157). In addition, in situ administration of SRA-silenced DCs enhances the effectiveness of local radiotherapy by provoking a robust systemic antitumor immunity (158).…”

Section: Hsp110 and Grp170-binding Receptors And Vaccine Designmentioning

confidence: 99%

High molecular weight stress proteins: Identification, cloning and utilisation in cancer immunotherapy

Wang

Subjeck

2013

International Journal of Hyperthermia

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Although the large stress/heat shock proteins (HSPs), i.e., Hsp110 and Grp170, were identified over 30 years ago, these abundant and highly conserved molecules have received much less attention compared to other conventional HSPs. Large stress proteins act as molecular chaperones with exceptional protein-holding capability and prevent the aggregation of proteins induced by thermal stress. The chaperoning properties of Hsp110 and Grp170 are integral to the ability of these molecules to modulate immune functions and are essential for developing large chaperone complex vaccines for cancer immunotherapy. The potent antitumor activity of the Hsp110/Grp170-tumor protein antigen complexes, demonstrated in preclinical studies, has led to a phase I clinical trial through the National Cancer Institute's RAID Program that is presently underway. Here we review aspects of the structure and function of these large stress proteins, their roles as molecular chaperones in the biology of cell stress, and prospects for their use in immune regulation and cancer immunotherapy. Lastly, we will discuss the recently revealed immunosuppressive activity of scavenger receptor A that binds to Hsp110 and Grp170, as well as the feasibility of targeting this receptor to promote T-cell activation and antitumor immunity induced by large HSP vaccines and other immunotherapies.

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“…30 The scavenger receptors, CD163 and CD204, are also expressed by DC subsets in some species. 43,87 Expression patterns of CD163 and CD204 in normal canine DCs have not been reported. Of the markers mentioned, only CD11b is not assessable in formalin-fixed tissues.…”

Section: Histiocytic Diseases Of Interstitial DC and Macrophage Originmentioning

confidence: 99%

A Review of Histiocytic Diseases of Dogs and Cats

2014

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Histiocytic proliferative disorders are commonly observed in dogs and less often cats. Histiocytic disorders occur in most of the dendritic cell (DC) lineages. Canine cutaneous histiocytoma originates from Langerhans cells (LCs) indicated by expression of CD1a, CD11c/CD18, and E-cadherin. When histiocytomas occur as multiple lesions in skin with optional metastasis to lymph nodes and internal organs, the disease resembles cutaneous Langerhans cell histiocytosis of humans. Langerhans cell disorders do not occur in feline skin. Feline pulmonary LCH has been recognized as a cause of respiratory failure due to diffuse pulmonary infiltration by histiocytes, which express CD18 and E-cadherin and contain Birbeck's granules. In dogs and cats, histiocytic sarcomas (HS) arise from interstitial DCs that occur in most tissues of the body. Histiocytic sarcomas begin as localized lesions, which rapidly disseminate to many organs. Primary sites include spleen, lung, skin, brain (meninges), lymph node, bone marrow, and synovial tissues of limbs. An indolent form of localized HS, progressive histiocytosis, originates in the skin of cats. Hemophagocytic HS originates in splenic red pulp and bone marrow macrophages in dogs and cats. In dogs, histiocytes in hemophagocytic HS express CD11d/CD18, which is a leuko-integrin highly expressed by macrophages in splenic red pulp and bone marrow. Canine reactive histiocytic diseases, systemic histiocytosis (SH) and cutaneous histiocytosis, are complex inflammatory diseases with underlying immune dysregulation. The lesions are dominated by activated interstitial DCs and lymphocytes, which invade vessel walls and extend as vasocentric infiltrates in skin, lymph nodes, and internal organs (SH).

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Targeting the Immunoregulator SRA/CD204 Potentiates Specific Dendritic Cell Vaccine-Induced T-cell Response and Antitumor Immunity

Cited by 50 publications

References 34 publications

Critical Role of AZI2 in GM-CSF–Induced Dendritic Cell Differentiation

Critical Role of AZI2 in GM-CSF–Induced Dendritic Cell Differentiation

High molecular weight stress proteins: Identification, cloning and utilisation in cancer immunotherapy

A Review of Histiocytic Diseases of Dogs and Cats

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