To achieve in situ tumor antigen uptake and presentation, intratumoral administration of ex vivo-generated, genemodified murine bone marrow-derived dendritic cells (DC) was used in a murine lung cancer model. To attract mature host DC and activated T cells at the tumor site, the DC were transduced with an adenoviral vector expressing secondary lymphoid tissue chemokine (CCL21/SLC). Sixty percent of the mice treated with 10 6 DC-AdCCL21 intratumorally (7-10 ng/ml/10 6 cells/24 h of CCL21) at weekly intervals for 3 weeks showed complete tumor eradication, whereas only 25% of mice had complete resolution of tumors when mice were treated with fibroblasts expressing CCL21. In contrast only 12% of the mice treated with unmodified or control vector modified DC (DC-AdCV) showed complete tumor eradication. DC-AdCCL21 administration led to increases in the CD4 ؉ , CD8 ؉ , and CD3 ؉ CXCR3 ؉ T cells, as well as DC expressing CD11c ؉ DEC205 ؉ . CD4 ؉ CD25 ؉ T-regulatory cells infiltrating the tumors were markedly reduced after DC-AdCCL21 therapy. The tumor site cellular infiltrates were accompanied by the enhanced elaboration of granulocyte macrophage colony-stimulating factor, IFN-␥, MIG/CXCL9, IP-10/CXCL10, and interleukin 12, but decreases in the immunosuppressive mediators transforming growth factor  and prostaglandin E 2 . DC-AdCCL21-treated tumor-bearing mice showed enhanced frequency of tumor-specific T lymphocytes secreting IFN-␥, and tumor protective immunity was induced after DC-AdCCL21 therapy. In vivo depletion of IP-10/CXCL10, MIG/CXCL9, or IFN-␥ significantly reduced the antitumor efficacy of DCAdCCL21. These findings provide a strong rationale for the evaluation of DC-AdCCL21 in cancer immunotherapy.
Thoracoscopic treatment of pulmonary sequestration is feasible in experienced hands. The aberrant systemic artery can be freed and dissected safely despite the frequently occurring inflammatory changes. Conversion rate to thoracotomy is low.
Clinically relevant bronchial anastomotic complications after LuTx can be avoided by use of a simple standardized surgical technique. Aggressive antibiotic and antifungal therapy might play an important supportive role.
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