In-vitro activation of natural killer cells from regional lymph nodes of melanoma patients with interleukin-2 and interleukin-15
2015
Аутори:
Vuletić, AnaJovanić, Irena P.
Jurišić, Vladimir B.
Milovanović, Zorka M.
Nikolić, Srdan S.
Tanić, Nikola
Konjević, Gordana M.
Тип документа:
Чланак у часопису (Објављена верзија)
,
© 2015 Wolters Kluwer Health, Inc.
Метаподаци
Приказ свих података о документуАпстракт:
Regional lymph nodes (LNs) represent the first barrier in lymphogenic
tumor dissemination in melanoma. Natural killer (NK) cells, the effector
cell subpopulation of the innate immune system, are in the first line of
antitumor immune defense. Therefore, the aim of this study was to
investigate the effect of interleukin (IL)-2 and IL-15, two cytokines
with similar immune-enhancing effects, on antitumor cytotoxic function
and immunophenotype of NK cells from regional LNs of melanoma patients.
Mononuclear cells purified from regional LNs of 50 melanoma patients in
clinical stage II-IV were treated in vitro for 72 h and 7 days with 200
IU/ml rhIL-2 and 25 ng/ml IL-15 at 37 degrees C in 5\% CO2. Both
cytokines significantly augmented NK cell cytotoxic activity,
transcription of the cytotoxic molecule perforin, and the level of
functionally mature perforin in both nonmetastatic and metastatic
regional LNs. IL-2 treatment increased the percentage of CD3(-)CD56(+)
NK cells by increasing the CD56(bright) NK cell subset in both
nonmetastatic and metastatic LNs, whereas IL-15 treatment did not affect
the percentage of NK cells and their subsets. Both cytokines increased
on NK cells from nonmetastatic and metastatic LNs the expression of CD69
early activation antigen, the NKG2D activating receptor, as well as CD16
and inhibitory killer-cell immunoglobulin-like receptor CD158b, both
inherent to the mature and the cytotoxic NK cell phenotype. In
conclusion, our data may indicate the therapeutic potential of the NK
cell population from regional LNs either as immunotherapeutic targets or
as adoptively transferred after activation with IL-2 or IL-15.
Кључне речи:
cytotoxicity; interleukin-15; interleukin-2; killer-cell immunoglobulin-like receptor; lymph nodes; melanoma; natural killer cells; perforinИзвор:
Melanoma Research, 2015, 25, 1, 22-34
DOI: 10.1097/CMR.0000000000000126
ISSN: 1473-5636