PMID- 30658847
OWN - NLM
STAT- In-Data-Review
LR  - 20190329
IS  - 1095-6859 (Electronic)
IS  - 0090-8258 (Linking)
VI  - 153
IP  - 1
DP  - 2019 Apr
TI  - Cytokine-induced memory-like natural killer cells have enhanced function,
      proliferation, and in vivo expansion against ovarian cancer cells.
PG  - 149-157
LID - S0090-8258(19)30039-3 [pii]
LID - 10.1016/j.ygyno.2019.01.006 [doi]
AB  - OBJECTIVE: Natural killer (NK) cells are lymphocytes well suited for adoptive
      immunotherapy. Attempts with adoptive NK cell immunotherapy against ovarian
      cancer have proven unsuccessful, with the main limitations including failure to
      expand and diminished effector function. We investigated if incubation of NK
      cells with interleukin (IL)-12, IL-15, and IL-18 for 16h could produce
      cytokine-induced memory-like (CIML) NK cells capable of enhanced function against
      ovarian cancer. METHODS: NK cells were preactivated briefly with IL-12, IL-15,
      and IL-18, rested, then placed against ovarian cancer targets to assess phenotype
      and function via flow cytometry. Real-time NK-cell-mediated tumor-killing was
      evaluated. Using ascites cells and cell-free ascites fluid, NK cell proliferation
      and function within the immunosuppressive microenvironment was evaluated in
      vitro. Finally, CIML NK cells were injected intraperitoneal (IP) into an in vivo 
      xenogeneic mouse model of ovarian cancer. RESULTS: CIML NK cells demonstrate
      enhanced cytokine (IFN-gamma) production and NK-cell-mediated killing of ovarian 
      cancer. NK cells treated overnight with cytokines led to robust activation
      characterized by temporal shedding of CD16, induction of CD25, and enhanced
      proliferation. CIML NK cells proliferate more with enhanced effector function
      compared to controls in an immunosuppressive microenvironment. Finally, human
      CIML NK cells exhibited potent antitumor effects within a xenogeneic mouse model 
      of ovarian cancer. CONCLUSIONS: CIML NK cells have enhanced functionality and
      persistence against ovarian cancer in vitro and in vivo, even when exposed to
      ascites fluid. These findings provide a strategy for NK cell-based immunotherapy 
      to circumvent the immunosuppressive nature of ovarian cancer.
CI  - Copyright (c) 2019. Published by Elsevier Inc.
FAU - Uppendahl, Locke D
AU  - Uppendahl LD
AD  - Department of Obstetrics, Gynecology and Women's Health, Division of Gynecologic 
      Oncology, University of Minnesota, Minneapolis, MN, United States.
FAU - Felices, Martin
AU  - Felices M
AD  - Department of Medicine, Division of Hematology, Oncology, and Transplantation,
      University of Minnesota, Minneapolis, MN, United States.
FAU - Bendzick, Laura
AU  - Bendzick L
AD  - Department of Obstetrics, Gynecology and Women's Health, Division of Gynecologic 
      Oncology, University of Minnesota, Minneapolis, MN, United States.
FAU - Ryan, Caitlin
AU  - Ryan C
AD  - Department of Obstetrics, Gynecology and Women's Health, Division of Gynecologic 
      Oncology, University of Minnesota, Minneapolis, MN, United States.
FAU - Kodal, Behiye
AU  - Kodal B
AD  - Department of Medicine, Division of Hematology, Oncology, and Transplantation,
      University of Minnesota, Minneapolis, MN, United States.
FAU - Hinderlie, Peter
AU  - Hinderlie P
AD  - Department of Medicine, Division of Hematology, Oncology, and Transplantation,
      University of Minnesota, Minneapolis, MN, United States.
FAU - Boylan, Kristin L M
AU  - Boylan KLM
AD  - Department of Laboratory Medicine and Pathology, University of Minnesota,
      Minneapolis, MN, United States.
FAU - Skubitz, Amy P N
AU  - Skubitz APN
AD  - Department of Laboratory Medicine and Pathology, University of Minnesota,
      Minneapolis, MN, United States.
FAU - Miller, Jeffrey S
AU  - Miller JS
AD  - Department of Medicine, Division of Hematology, Oncology, and Transplantation,
      University of Minnesota, Minneapolis, MN, United States.
FAU - Geller, Melissa A
AU  - Geller MA
AD  - Department of Obstetrics, Gynecology and Women's Health, Division of Gynecologic 
      Oncology, University of Minnesota, Minneapolis, MN, United States. Electronic
      address: gelle005@umn.edu.
LA  - eng
GR  - P50 CA136393/CA/NCI NIH HHS/United States
GR  - R21 CA150085/CA/NCI NIH HHS/United States
GR  - R35 CA197292/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20190115
PL  - United States
TA  - Gynecol Oncol
JT  - Gynecologic oncology
JID - 0365304
PMC - PMC6430659
MID - NIHMS1518836
EDAT- 2019/01/20 06:00
MHDA- 2019/01/20 06:00
CRDT- 2019/01/20 06:00
PMCR- 2020/04/01 00:00
PHST- 2018/09/26 00:00 [received]
PHST- 2018/12/12 00:00 [revised]
PHST- 2019/01/03 00:00 [accepted]
PHST- 2020/04/01 00:00 [pmc-release]
PHST- 2019/01/20 06:00 [pubmed]
PHST- 2019/01/20 06:00 [medline]
PHST- 2019/01/20 06:00 [entrez]
AID - S0090-8258(19)30039-3 [pii]
AID - 10.1016/j.ygyno.2019.01.006 [doi]
PST - ppublish
SO  - Gynecol Oncol. 2019 Apr;153(1):149-157. doi: 10.1016/j.ygyno.2019.01.006. Epub
      2019 Jan 15.