Cytolytic activities of IL-2 activated NK cells from MMTV/v-Ha-ras transgenic oncomice during tumor progression.
IL-2 activated natural killer (A-NK) cells have the capacity to infiltrate metastatic tumors and lyse tumor cells. Nevertheless, adoptive immunotherapy with lymphokine-activated killer cells has been only modestly effective in the clinic and has not routinely provided long-term survival in patients with established cancer metastases. This may indicate the need for more carefully investigating the role of effector cells of the immune response, including A-NK cells, in models of tumor progression. Herein we describe the use of the MMTV/v-Ha-ras transgenic mouse model as a system for exploring the role of NK cells during tumor progression. We have examined the lytic capacity of A-NK cells generated from tumor-free and tumor-bearing transgenic oncomice against standard A-NK cell targets (YAC-1 and P815) in addition to tumor cells isolated from these animals. A-NK cells generated from mice without obvious tumor burden show higher lytic activity than A-NK cells generated from mice with evident tumors, i.e., those at a more advanced stage of tumor progression. Only long term (8-day) cultures of late passage A-NK cells generated from tumor-bearing mice showed significant increases in lytic activity over those generated from tumor-free mice. These results suggest that experimental protocols using transgenic oncomice at various stages of tumor growth may constitute a novel model for testing the role of A-NK cells for their capacity to interfere with cancer progression.
Goldfarb
R H
RH
Department of Molecular Biology and Immunology, University of North Texas Health Science Center at Fort Worth 76107, USA.
Albertsson
P
P
Nannmark
U
U
Kitson
R P
RP
D000818:Animals; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D018450:Disease Progression; D011905:Genes, ras / Q000235:genetics*; D015979:Killer Cells, Lymphokine-Activated / Q000201:enzymology / Q000502:physiology*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology*; D010447:Peptide Hydrolases / Q000378:metabolism; D013997:Time Factors
D010447:Peptide Hydrolases