Graft Site Microenvironment Determines Dendritic Cell Trafficking Through the CCR7-CCL19/21 Axis

Hua, Jing; Stevenson, William; Dohlman, Thomas H.; Inomata, Takenori; Tahvildari, Maryam; Calcagno, Narghes; Pirmadjid, Negar; Sadrai, Zahra; Chauhan, Sunil; Dana, Reza

doi:10.1167/iovs.15-17551

Cited by 27 publications

(18 citation statements)

References 46 publications

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“…The detected transcripts encoded chemokines ( CCL‐3, CCL‐4, CCL‐5, CCL‐19, CCL‐20 and CCL‐21 ), cytokines ( IL‐2, IFN‐γ, TNF‐α and GM‐CSF ) and immune modulating factors in the tumour microenvironment (VEG‐F, SDF‐1, FAP, MMP‐9, IL‐10 and PDL‐1) . Primers and other details have been described in previously published reports by our group and others . qRT‐PCR data were analysed using the comparative Ct method, and expression levels of target genes were normalized to β‐actin levels in each tissue sample.…”

Section: Methodsmentioning

confidence: 99%

MUC1‐ and Survivin‐based DNA Vaccine Combining Immunoadjuvants CpG and interleukin‐2 in a Bicistronic Expression Plasmid Generates Specific Immune Responses and Antitumour Effects in a Murine Colorectal Carcinoma Model

et al. 2018

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DNA vaccination is a promising cancer treatment due to its safety, but poor immunogenicity limits its application. However, immunoadjuvants, heterogeneous prime-boost strategies and combination with conventional treatments can be used to improve the antitumour immune effects. A CpG motif and interleukin-2 (IL-2) cytokine are often used as adjuvants. In this study, a DNA vaccine containing a CpG motif was constructed to evaluate its adjuvant effect. The results show that the cytotoxicity of the DNA vaccine was increased fivefold, and survival lifetime was prolonged twofold by the CpG motif adjuvant. To simplify the industrial production process, a bicistronic plasmid was constructed to carry the fusion genes of survivin/MUC1 (MS) and IL-2 and with a CpG motif in its backbone. The results showed that the antitumour effect of the bicistronic vaccine was the same as that of the two vaccine co-injected regime. Furthermore, the vaccine could suppress metastatic tumour foci by 69.1% in colorectal carcinoma-bearing mice. Moreover, the vaccine induced survivin- and MUC1-specific immune responses in splenocytes and induced the immune promoting factor CCL-19 and GM-CSF upregulated, while metastatic-associated factor MMP-9 and immunosuppressing factor PD-L1 downregulated in tumour tissue. When combining the vaccine with the chemotherapy drug oxaliplatin, the survival was prolonged by about 2.5-fold. In conclusion, the DNA vaccine containing a CpG motif in bicistronic form showed good effects on colorectal cancer by inhibiting both tumour growth and metastasis, and combination with oxaliplatin could improve its antitumour effects.

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Section: Methodsmentioning

confidence: 99%

MUC1‐ and Survivin‐based DNA Vaccine Combining Immunoadjuvants CpG and interleukin‐2 in a Bicistronic Expression Plasmid Generates Specific Immune Responses and Antitumour Effects in a Murine Colorectal Carcinoma Model

et al. 2018

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“…Recent studies have alluded to the role of DCs as biomarkers for corneal epithelial inflammation in patients with type 2 diabetes mellitus, suggesting they may also be used as biomarkers for graft-related inflammation [56]. Nuanced variations in the presence, phenotype, and maturity of APC and DC populations have been shown to have varying associations on corneal allograft transplantation outcomes, implying they may reveal underlying immune dynamics [16,57,58]. Hamrah et al reported that the number and distribution of mature CD11c+ DC populations is increased in the anterior stroma and that there is an upregulation of MHC class II molecules within 24 h after inflammation is induced.…”

Section: Major Histocompatibility Complex and Antigen-presenting Cellsmentioning

confidence: 99%

Variable Responses to Corneal Grafts: Insights from Immunology and Systems Biology

Zazzo

Lee

Sung

et al. 2020

JCM

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Corneal grafts interact with their hosts via complex immunobiological processes that sometimes lead to graft failure. Prediction of graft failure is often a tedious task due to the genetic and nongenetic heterogeneity of patients. As in other areas of medicine, a reliable prediction method would impact therapeutic decision-making in corneal transplantation. Valuable insights into the clinically observed heterogeneity of host responses to corneal grafts have emerged from multidisciplinary approaches, including genomics analyses, mechanical studies, immunobiology, and theoretical modeling. Here, we review the emerging concepts, tools, and new biomarkers that may allow for the prediction of graft survival.

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“…However, current methods used to stimulate lymphangiogenesis require an inflammatory insult, which in and of itself may trigger augmented DC migration. Work from our group and others helped to reveal the role of CC-chemokine receptor 7 (CCR7) in migration of corneal DCs to the lymph nodes 29, 46, 65, 66, 67, 68 , which could be another way that DC migration may be regulated independently of lymphangiogenesis 66 . Corneal abrasion was also demonstrated to increase antigen drainage to the lymph nodes, signifying a key role for the epithelium in maintaining immune privilege 69 .…”

Section: Eye Immune Privilege Breach and The Mpsmentioning

confidence: 99%

New insights into mononuclear phagocyte biology from the visual system

2017

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Major advances in mononuclear phagocyte biology have been realized, yet key questions pertinent to health and disease remain, including in the visual system. One problem concerns how dendritic cells can trigger immune responses from certain tightly regulated immune privileged sites of the eye. Another, albeit separate, problem involves whether functional specializations exist for microglia versus monocytes in neurodegenerating retinas. We examine novel insights in eye immune privilege and, separately, review recent inroads concerning retinal degeneration. Both themes have been extensively studied in the visual system, and exhibit parallels highlighted here with recent findings in CNS mononuclear phagocytes and in the periphery.

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Graft Site Microenvironment Determines Dendritic Cell Trafficking Through the CCR7-CCL19/21 Axis

Cited by 27 publications

References 46 publications

MUC1‐ and Survivin‐based DNA Vaccine Combining Immunoadjuvants CpG and interleukin‐2 in a Bicistronic Expression Plasmid Generates Specific Immune Responses and Antitumour Effects in a Murine Colorectal Carcinoma Model

MUC1‐ and Survivin‐based DNA Vaccine Combining Immunoadjuvants CpG and interleukin‐2 in a Bicistronic Expression Plasmid Generates Specific Immune Responses and Antitumour Effects in a Murine Colorectal Carcinoma Model

Variable Responses to Corneal Grafts: Insights from Immunology and Systems Biology

New insights into mononuclear phagocyte biology from the visual system

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