Adoptive transfer of natural killer cells promotes the anti-tumor efficacy of T cells

Adoptive transfer of natural killer cells promotes the anti-tumor efficacy of T cells

Copyright © 2016 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 177(2017) vom: 05. Apr., Seite 76-86
1. Verfasser: Goding, Stephen R (VerfasserIn)
Weitere Verfasser: Yu, Shaohong, Bailey, Lisa M, Lotze, Michael T, Basse, Per H
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2017
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Research Support, Non-U.S. Gov't Adoptive cell transfer Cancer immunotherapy Cell traffic Cytotoxic T lymphocytes (CTL) Cytotoxicity Natural killer cells (NK cells) mehr... Cytokines Ovalbumin 9006-59-1
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100 1 |a Goding, Stephen R  |e verfasserin  |4 aut 
245 1 0 |a Adoptive transfer of natural killer cells promotes the anti-tumor efficacy of T cells 
264 1 |c 2017 
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520 |a Copyright © 2016 Elsevier Inc. All rights reserved. 
520 |a The density of NK cells in tumors correlates positively with prognosis in many types of cancers. The average number of infiltrating NK cells is, however, quite modest (approximately 30 NK cells/sq.mm), even in tumors deemed to have a "high" density of infiltrating NK cells. It is unclear how such low numbers of tumor-infiltrating NK cells can influence outcome. Here, we used ovalbumin-expressing tumor cell lines and TCR transgenic, OVA-specific cytotoxic T lymphocytes (OT-I-CTLs) to determine whether the simultaneous attack by anti-tumor CTLs and IL-2-activated NK (A-NK) cells synergistically increases the overall tumor cell kill and whether upregulation of tumor MHC class-I by NK cell-derived interferon-gamma (IFNγ) improves tumor-recognition and kill by anti-tumor CTLs. At equal E:T ratios, A-NK cells killed OVA-expressing tumor cells better than OT-I-CTLs. The cytotoxicity against OVA-expressing tumor cells increased by combining OT-I-CTLs and A-NK cells, but the increase was additive rather than synergistic. A-NK cells adenovirally-transduced to produce IL-12 (A-NKIL-12) produced high amounts of IFNγ. The addition of a low number of A-NKIL-12 cells to OT-I-CTLs resulted in a synergistic, albeit modest, increase in overall cytotoxicity. Pre-treatment of tumor cells with NK cell-conditioned medium increased tumor MHC expression and sensitivity to CTL-mediated killing. Pre-treatment of CTLs with NK cell-conditioned medium had no effect on CTL cytotoxicity. In vivo, MHC class-I expression by OVA-expressing B16 melanoma lung metastases increased significantly within 24-48h after adoptive transfer of A-NKIL-12 cells. OT-I-CTLs and A-NKIL-12 cells localized selectively and equally well into OVA-expressing B16 lung metastases and treatment of mice bearing 7-days-old OVA-B16 lung metastases with both A-NKIL-12 cells and OT-I-CTLs lead to a significant prolongation of survival. Thus, an important function of tumor-infiltrating NK cells may be to increase tumor cell expression of MHC class-I through secretion of IFNγ, to prepare them for recognition by tumor-specific CTLs 
650 4 |a Journal Article 
650 4 |a Research Support, N.I.H., Extramural 
650 4 |a Research Support, U.S. Gov't, Non-P.H.S. 
650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a Adoptive cell transfer 
650 4 |a Cancer immunotherapy 
650 4 |a Cell traffic 
650 4 |a Cytotoxic T lymphocytes (CTL) 
650 4 |a Cytotoxicity 
650 4 |a Natural killer cells (NK cells) 
650 7 |a Cytokines  |2 NLM 
650 7 |a Ovalbumin  |2 NLM 
650 7 |a 9006-59-1  |2 NLM 
700 1 |a Yu, Shaohong  |e verfasserin  |4 aut 
700 1 |a Bailey, Lisa M  |e verfasserin  |4 aut 
700 1 |a Lotze, Michael T  |e verfasserin  |4 aut 
700 1 |a Basse, Per H  |e verfasserin  |4 aut 
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773 1 8 |g volume:177  |g year:2017  |g day:05  |g month:04  |g pages:76-86 
856 4 0 |u http://dx.doi.org/10.1016/j.clim.2016.06.013  |3 Volltext 
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