RETINOIDS, BREAST-CANCER AND NK CELLS

Citation
Ml. Villa et al., RETINOIDS, BREAST-CANCER AND NK CELLS, British Journal of Cancer, 68(5), 1993, pp. 845-850
Citations number
13
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology
Journal title
ISSN journal
0007-0920
Volume
68
Issue
5
Year of publication
1993
Pages
845 - 850
Database
ISI
SICI code
0007-0920(1993)68:5<845:RBANC>2.0.ZU;2-A
Abstract
N-(4-hydroxyphenyl) retinamide (4-HPR) is a synthetic retinoid which r educes the incidence of experimental tumours in animals and has been c hosen for its weak toxicity to be tested as a chemopreventive agent in humans. The mechanism of antineoplastic action is still unknown but a possible immunoenhancing effect may be postulated. We investigated th e NK activity of PBMC from a group of women treated with 4-HPR as a pa rt of a large scale randomised phase III trial on chemoprevention of c ontrolateral disease in mastectomised women. After 180 days of treatme nt the NK activity was augmented 1.73 times as compared to that of pat ients given a placebo. The NK activity of PBMC from 4-HPR treated wome n is maximised, being higher than the basal and even the rIL-2 or alfa -rIFN stimulated activity of controls. For this reason in the majority of cases it cannot be further augmented by incubation with either rIL -2 or alfa-rIFN in vitro. The increased NK activity of 4-HPR treated w omen is not due to an enhanced production of endogenous IL-2, because PBMC cultures from patients treated with 4-HPR or placebo, incubated i n vitro with a panel of different stimulators (recall antigens, PHA, a llogeneic and xenogeneic cells) produce similar amounts of IL-2. The f unctional activity, but not the number of NK cells is increased in 4-H PR treated women. The mechanism by which 4-HPR stimulates NK activity is not a function of direct action on NK cells. Indeed incubation of P BMC from blood donors with 4-HPR or its major metabolite N-(4-methoxyp henyl) retinamide (4-MPR) does not modify their natural cytotoxicity.