Activated Natural Killer Cell Tumor Retention and Cytokine Production in Colon Tumor Using a Tissue-Isolated Model

• Published in: The Journal of surgical research Vol. 82; no. 1; pp. 78 - 87
• Main Authors: Ribeiro, Ulysses, Whiteside, Theresa L., Basse, Per H., Safatle-Ribeiro, Adriana V., Huneke, Catherine E., Posner, Mitchell C.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01.03.1999; Elsevier
• Subjects: activated natural killer cells; Adoptive Transfer; Animals; Biological and medical sciences; colon tumor; Colonic Neoplasms - immunology; Colonic Neoplasms - pathology; Colonic Neoplasms - therapy; cytokines; Cytokines - biosynthesis; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunohistochemistry; interleukin-2; Killer Cells, Natural - immunology; Killer Cells, Natural - pathology; Killer Cells, Natural - transplantation; Medical sciences; Neoplasm Transplantation; Perfusion; Rats; Rats, Nude; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; tissue-isolated tumors; Transplantation, Heterologous; Tumor Cells, Cultured; Tumors; tissue-isolated tumors; interleukin-2; colon tumor; cytokines; perfusion; activated natural killer cells; Animal model; Rat; Pathogenesis; In situ; Rodentia; Cytokine; Exploration; Activation; Experimental study; Retention; Colonic disease; Infusion; Vertebrata; Mammalia; Ex vivo; Production; Digestive diseases; Intestinal disease; Tumor; Intraarterial administration; Killer cell; Colon
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1998.5521

Background.Adoptively transferred activated natural killer (A-NK) cells are capable of selectively infiltrating solid tumors, but only at low efficiency when administered systemically. It is unclear if human A-NK cells can be retained in tumor tissue and, if so, what is their action. We investigated intratumor A-NK cell retention andin situcytokine production, using an xenogeneicex vivotissue-isolated tumor model, which permits direct intraarterial infusion. Materials and Methods.Human colon adenocarcinoma (HT-29) was implanted in the ovarian fat pad of nude rats. The tumors were perfusedex vivo25 to 30 days postimplant with a known number of cells, and the effluent was collected over time. The number of human A-NK cells and cell surface antigen expression of cells infused and exiting the tumor were calculated, using cell counts and flow cytometry, respectively. Frozen sections were stained with Giemsa and also immunostained for the presence of interleukin-2, -4, and -10, tumor necrosis factor α (TNF-α), and interferon. Results.Six perfusions with 8 × 106A-NK cells were performed. The mean number of infused A-NK cells that remained in the tumor at the completion of perfusion was 4.74 × 106(59.2%). No differences were noted in cellular phenotype between the infused cells and the cells exiting the tumor: expression of the markers CD45 (97.5% vs 94.5%), CD14 (0 vs 0), CD3 (3.83% vs 2.83%), and CD56 (86% vs 83%) was unchanged,P> 0.05. Microscopic examination of tumor sections showed tumor surrounded by A-NK cells, with some tumor nests infiltrated by A-NK cells.In situimmunopositivity for interleukin-2 (2/6), interleukin-4 (3/6), interleukin-10 (2/6), and TNF-α (2/6) specimens was observed. Immunostaining for interferon-γ was negative. Conclusions.The retention of A-NK cells in the transplanted human colon tumor tissue was found to be efficient (59.2 %) in this model. Although perfusion time was limited, A-NK cells were able to infiltrate the tumor and initiate cytokine production.