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Improved efficacy of dendritic cell-based immunotherapy by cutaneous laser illumination.

ABSTRACT: The present study investigates a convenient laser-based approach to enhance dendritic cell (DC) migration and improve DC-based immunotherapy in murine models.Influence of laser illumination on dermal tissue microenvironment and migration of DCs following intradermal injection were determined by whole-mount immunohistochemistry, transmission electron microscope, and flow cytometry. We also investigated in vivo expansion of CTLs by flow cytometry, CTL activity by in vitro CTL assay, and antitumor efficacy of DC immunization following cutaneous laser illumination in both preventive and therapeutic tumor models.Laser illumination was found to significantly enlarge perforations in the perilymphatic basement membrane, disarray collagen fibers, and disrupt cell-matrix interactions in the dermis. The altered dermal tissue microenvironment permitted more efficient migration of intradermally injected DCs from the dermis to the draining lymph nodes (dLN). Laser illumination also slightly but significantly enhanced the expression of costimulatory molecule CD80 and MHC I on inoculated DCs. As a result, more vigorous expansion of tumor-specific IFN-?(+)CD8(+) T lymphocytes and enhanced CTL activity against 4T1 but not irrelevant tumor cells were obtained in the laser-treated group over the control group. Laser-augmented DC immunization also completely abrogated early growth of 4T1 tumor and B16F10 melanoma in preventive tumor models and significantly extended the survival of 4T1-resected mice in a therapeutic tumor model.These data suggest a simple, safe, laser-based approach to significantly enhance DC-based immunotherapy.

SUBMITTER: Chen X

PROVIDER: S-EPMC3328606 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Improved efficacy of dendritic cell-based immunotherapy by cutaneous laser illumination.

Chen Xinyuan X Zeng Qiyan Q Wu Mei X MX

Clinical cancer research : an official journal of the American Association for Cancer Research 20120305 8

<h4>Purpose</h4>The present study investigates a convenient laser-based approach to enhance dendritic cell (DC) migration and improve DC-based immunotherapy in murine models.<h4>Experimental design</h4>Influence of laser illumination on dermal tissue microenvironment and migration of DCs following intradermal injection were determined by whole-mount immunohistochemistry, transmission electron microscope, and flow cytometry. We also investigated in vivo expansion of CTLs by flow cytometry, CTL ac ...[more]

PMID: 22392913

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Project description:Acute and chronic myeloid leukemia (AML, CML) are hematologic malignancies arising from oncogene-transformed hematopoietic stem/progenitor cells known as leukemia stem cells (LSCs). LSCs are selectively resistant to various forms of therapy including irradiation or cytotoxic drugs. The introduction of tyrosine kinase inhibitors has dramatically improved disease outcome in patients with CML. For AML, however, prognosis is still quite dismal. Standard treatments have been established more than 20 years ago with only limited advances ever since. Durable remission is achieved in less than 30% of patients. Minimal residual disease (MRD), reflected by the persistence of LSCs below the detection limit by conventional methods, causes a high rate of disease relapses. Therefore, the ultimate goal in the treatment of myeloid leukemia must be the eradication of LSCs. Active immunotherapy, aiming at the generation of leukemia-specific cytotoxic T cells (CTLs), may represent a powerful approach to target LSCs in the MRD situation. To fully activate CTLs, leukemia antigens have to be successfully captured, processed, and presented by mature dendritic cells (DCs). Myeloid progenitors are a prominent source of DCs under homeostatic conditions, and it is now well established that LSCs and leukemic blasts can give rise to "malignant" DCs. These leukemia-derived DCs can express leukemia antigens and may either induce anti-leukemic T cell responses or favor tolerance to the leukemia, depending on co-stimulatory or -inhibitory molecules and cytokines. This review will concentrate on the role of DCs in myeloid leukemia immunotherapy with a special focus on their generation, application, and function and how they could be improved in order to generate highly effective and specific anti-leukemic CTL responses. In addition, we discuss how DC-based immunotherapy may be successfully integrated into current treatment strategies to promote remission and potentially cure myeloid leukemias.

Dataset Information

Improved efficacy of dendritic cell-based immunotherapy by cutaneous laser illumination.

Publications

Improved efficacy of dendritic cell-based immunotherapy by cutaneous laser illumination.

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