| Enhancement of antitumor immunity by combining anti-cytotoxic T lymphocyte antigen-4 antibodies and cryotreated tumor lysate-pulsed dendritic cells in murine osteosarcoma. | |
| | |
MedLine Citation:
|
PMID: 23291864 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Immunotherapy with tumor lysate-loaded dendritic cells (DCs) is one of the most promising strategies to induce antitumor immune responses. However, the antitumor activity of cytotoxic T cells may be restrained by their expression of the inhibitory T-cell coreceptor cytotoxic T lymphocyte antigen-4 (CTLA-4). By relieving this restraint, CTLA-4-blocking antibodies promote tumor rejection, but the full scope of their most suitable applications has yet to be fully determined. In the present study, we offer proof of a preclinical concept in a C3H mouse osteosarcoma (LM8) model that CTLA-4 blockade cooperates with cryotreated tumor lysate-pulsed DCs in a primary tumor to prevent the outgrowth of lung metastasis. To evaluate immune response activation, we established the following four groups of C3H mice (60 mice in total): i) control immunoglobulin G (IgG)-treated mice; ii) tumor lysate-pulsed DC-treated mice; iii) anti-CTLA-4 antibody-treated mice and iv) tumor lysate-pulsed DC- and anti-CTLA-4 antibody-treated mice. The mice that received the tumor lysate-pulsed DCs and anti-CTLA-4 antibody displayed reduced numbers of regulatory T lymphocytes and increased numbers of CD8+ T lymphocytes inside the metastatic tumor, inhibition of metastatic growth, a prolonged lifetime, reduced numbers of regulatory T lymphocytes in the spleen and high serum interferon-γ levels. Combining an anti-CTLA-4 antibody with tumor lysate-pulsed DCs enhanced the systemic immune response. To the best of our knowledge, these findings document for the first time an effect of the combination of tumor lysate-pulsed DCs and CTLA-4-blocking antibodies in osteosarcoma. We suggest that cryotreated tumor lysate-pulsed DCs, although insufficient on their own, may mediate the rejection of metastatic lesions and prevent recurrence of the disease when combined with CTLA-4 blockade in osteosarcoma patients in the clinical setting. |
| | |
Authors:
|
Masanori Kawano; Ichiro Itonaga; Tatsuya Iwasaki; Hiroshi Tsumura |
Related Documents
:
|
17945324 - Arsenic promotes centrosome abnormalities and cell colony formation in p53 compromised ... 11280384 - Immunohistochemical detection of tumor suppressor gene p53 protein in feline injection ... 3060794 - Meth a fibrosarcoma cells express two transforming mutant p53 species. 15004514 - Gene expression profiling of p53-sensitive and -resistant tumor cells using dna microar... 12101854 - Cardiac tamponade caused by intrapericardial yolk sac tumor in a boy. 3889804 - Neuroblastoma. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2013-1-04 |
Journal Detail:
|
Title: Oncology reports Volume: - ISSN: 1791-2431 ISO Abbreviation: Oncol. Rep. Publication Date: 2013 Jan |
Date Detail:
|
Created Date: 2013-1-7 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9422756 Medline TA: Oncol Rep Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Department of Orthopaedic Surgery, Faculty of Medicine, Oita University, Oita 879-5593, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Expression of anti-Mullerian hormone receptor on the appendix testis in connection with urological d...
Next Document: Neurological Complications Associated With HIV and AIDS: Clinical Implications for Nursing.