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Paper Information

Title: 

THE EFFECT OF HYPOXIA ON NUTURAL KILLER ACTIVITY OF HUMAN PBLS AGAINST PROSTATE TUMOR DU-145 AND MYELOID LEUKEMIA K562 CELL LINES

Type: PAPER
Author(s): SHEYKHI A.A.K.*,GRAHAM CH.,PROSS H.,SIEMENS D.R.
 
 *DEPARTMENTS OF IMMUNOLOGY, SCHOOL OF MEDICINE, ZANJAN UNIVERSITY OF MEDICAL SCIENCES, ZANJAN, IRAN
 
Name of Seminar: BIENNIAL CONGRESS ON IMMUNOLOGY, ASTHMA AND ALLERGY
Type of Seminar:  CONGRESS
Sponsor:  IRAN UNIVERSITY OF MEDICAL SCIENCES AND HEALTH SERVICES
Date:  2007Volume 6
 
 
Abstract: 

Tumour hypoxia is associated with malignant progression and a poor clinical outcome for patients with avariety of cancers. An important aspect of malignant progression is the ability of tumor cells to evade immune detection and killing. We previously showed that certain adaptive responses of tumor cells to hypoxia, i. e. drug resistance, invasion metastasis, can be inhibited by activating nitric oxide (NO) signaling via administration of low concentrations of NO mimetic agents. Thus the aim of the present study was to determine if exposure of tumor cells to hypoxia renders them less susceptible to killing by NK cells and, if so, whether such effect of hypoxia can be prevented by the NO mimetic glyceryl trinitrate (GTN). A [51Cr]-release assay was used to determine NK activity against tumor cells. Results revealed that pre-incubation of the metastatic DU-145 prostate cancer cell line and the highly NK-sensitive K562 cell line (target cells) in 1% O2 (vs. 20% O2) for 24h resulted in increased resistance to the NK killing activity of fresh or interleukin-2 activated peripheral blob lymphocytes (PBLs). When the hypoxic pre-incubation was performed in the presence of GTN (1nM), the resistance to the NK killing was significantly decreased. These results indicate that tumor hypoxia may contribute to malignant progression by increasing the ability of tumor cells to evade NK activity. The findings also suggest that NO mimetics may be used as potential adjuvants to immunotherapy. (Supported by the "Ride for Dad" Prostate Cancer Fund).

 
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