PMID- 29750425
OWN - NLM
STAT- MEDLINE
DCOM- 20181002
LR  - 20181004
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 53
IP  - 1
DP  - 2018 Jul
TI  - Increased infiltration of macrophages to radioresistant lung cancer cells
      contributes to the development of the additional resistance of tumor cells to the
      cytotoxic effects of NK cells.
PG  - 317-328
LID - 10.3892/ijo.2018.4394 [doi]
AB  - In this study, in order to investigate the effects of increased macrophage
      infiltration to radioresistant lung tumors in regulating natural killer (NK)
      cell-mediated immunity, we examined whether the treatment of radioresistant cells
      with conditioned medium (CM) from phorbol myristate acetate (PMA)/interleukin
      (IL)-4 treated THP-1 cells (used as a tumor-associated macrophage source) leads
      to the development of the additional resistance of tumor cells to NK cell
      cytotoxicity. We found that the susceptibility of THP-1 CM-treated radioresistant
      cells to NK cell cytotoxicity was decreased compared to the non-treated cells. In
      addition, it was found that such a decreased susceptibility was associated with
      increased programmed death receptor ligand 1 (PD-L1) and decreased natural killer
      group 2D (NKG2D) ligand levels in tumor cells. We further discovered that the
      THP-1 cells secreted a high level of IL-6, and that blocking IL-6 action by the
      addition of a neutralizing antibody (Ab) for IL-6 into the THP-1 CM decreased the
      resistance of THP-1 CM-treated radioresistant cells to NK cell cytotoxicity.
      Moreover, we discovered that MEK/Erk was the most critical IL-6 downstream
      signaling pathway in triggering the THP-1 CM effect; thus, the addition of
      MEK/Erk inhibitor to THP-1 CM enhanced the susceptibility of the THP-1 CM-treated
      radioresistant cells to NK cell cytotoxicity. On the whole, the findings of this 
      study suggest the existence of a malignant loop characterized by increased
      macrophage infiltration into radioresistant cells which, in turn, promotes the
      development of the additional resistance of these cells to NK cell cytotoxicity.
FAU - Shen, Mingjing
AU  - Shen M
AD  - Department of Radiation Oncology, University of Rochester School of Medicine and 
      Dentistry, Rochester, NY 14642, USA.
FAU - Chen, Yongbing
AU  - Chen Y
AD  - Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Soochow
      University, Suzhou, Jiangsu 215004, P.R. China.
FAU - Xu, Lijun
AU  - Xu L
AD  - Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Soochow
      University, Suzhou, Jiangsu 215004, P.R. China.
FAU - Zhu, Rongying
AU  - Zhu R
AD  - Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Soochow
      University, Suzhou, Jiangsu 215004, P.R. China.
FAU - Xue, Xiang
AU  - Xue X
AD  - Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Soochow
      University, Suzhou, Jiangsu 215004, P.R. China.
FAU - Tsai, Ying
AU  - Tsai Y
AD  - Department of Radiation Oncology, University of Rochester School of Medicine and 
      Dentistry, Rochester, NY 14642, USA.
FAU - Keng, Peter C
AU  - Keng PC
AD  - Department of Radiation Oncology, University of Rochester School of Medicine and 
      Dentistry, Rochester, NY 14642, USA.
FAU - Lee, Soo Ok
AU  - Lee SO
AD  - Department of Radiation Oncology, University of Rochester School of Medicine and 
      Dentistry, Rochester, NY 14642, USA.
FAU - Chen, Yuhchyau
AU  - Chen Y
AD  - Department of Radiation Oncology, University of Rochester School of Medicine and 
      Dentistry, Rochester, NY 14642, USA.
LA  - eng
PT  - Journal Article
DEP - 20180504
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (CD274 protein, human)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Interleukin-6)
RN  - 0 (KLRK1 protein, human)
RN  - 0 (Ligands)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily K)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Antibodies, Neutralizing/immunology/pharmacology
MH  - B7-H1 Antigen/immunology
MH  - Cell Proliferation/radiation effects
MH  - Culture Media, Conditioned/chemistry/pharmacology
MH  - Cytotoxicity, Immunologic/*immunology
MH  - Humans
MH  - Interleukin-6/antagonists & inhibitors/immunology
MH  - Killer Cells, Natural/*immunology
MH  - Ligands
MH  - Lung Neoplasms/*immunology/pathology/radiotherapy
MH  - Macrophages/drug effects/*immunology/pathology
MH  - NK Cell Lectin-Like Receptor Subfamily K/immunology
MH  - Neoplastic Stem Cells/immunology
MH  - Radiation Tolerance/*immunology
MH  - Signal Transduction/drug effects
MH  - Tetradecanoylphorbol Acetate/chemistry/pharmacology
EDAT- 2018/05/12 06:00
MHDA- 2018/10/03 06:00
CRDT- 2018/05/12 06:00
PHST- 2017/11/10 00:00 [received]
PHST- 2018/04/02 00:00 [accepted]
PHST- 2018/05/12 06:00 [pubmed]
PHST- 2018/10/03 06:00 [medline]
PHST- 2018/05/12 06:00 [entrez]
AID - 10.3892/ijo.2018.4394 [doi]
PST - ppublish
SO  - Int J Oncol. 2018 Jul;53(1):317-328. doi: 10.3892/ijo.2018.4394. Epub 2018 May 4.