Nl. Vujanovic et al., ANTITUMOR ACTIVITIES OF SUBSETS OF HUMAN IL-2-ACTIVATED NATURAL-KILLER-CELLS IN SOLID TISSUES, The Journal of immunology, 154(1), 1995, pp. 281-289
Human NK cells can be separated into two functionally distinct subpopu
lations based on the ability to rapidly respond to IL-2 by adherence t
o solid surfaces. To determine functions of the NK cell subsets in sol
id tumor tissues, adherent (A) and nonadherent (NA) NK cells were eval
uated for their ability to infiltrate multicellular tumor spheroids in
vitro, to kill carcinoma (CA) cell targets in these spheroids, and to
mediate antitumor activity in vivo. A-NK cells were less cytolytic th
an NA-NK cells against CA targets in single cell suspensions or in mon
olayers. However, A-NK cells showed a significantly better ability tha
n NA-NK cells to infiltrate tumor tissues and kill tumor cells in sphe
roids of human squamous cell CA of the head and neck or breast CA. Per
ilesional delivery of human A-NK cells and IL-2 resulted in regression
of established human squamous cell carcinoma of the head and neck tum
ors growing subcutaneously in immunosuppressed nude mice. Similarly, i
n a xenograft model of human gastric CA metastatic to liver of nude mi
ce, a single intrasplenic injection of A-NK cells in combination with
i.p. infusions of IL-2 significantly reduced the number of established
hepatic metastases (p < 0.007) and prolonged survival of the mice (p
< 0.003). In contrast, NA-NK cells were ineffective in either of the i
n vivo xenograft tumor models. These findings demonstrate that A-NK ce
lls represent a biologically unique and important subset of NK cells t
hat, in contrast to the rest of NK cells, function as effector cells i
n solid tumor tissues and, consequently, have a great antitumor therap
eutic potential.