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In vitro -induced M2 type macrophages induces the resistance of prostate cancer cells to cytotoxic action of NK cells
- Source :
- Experimental Cell Research. 364:113-123
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Previous reports, including our experimental results, showed that macrophages migrate to prostate cancer (PCa) cells. We tested whether the migrated macrophages affect the susceptibility of castration-resistant PCa (CRPC) cells to cytotoxic actions of natural killer (NK) cells. We found treatment of tumor cells with the conditioned media (CM) of the PMA/IL-4 treated THP-1 cells (M2 type macrophages) (THP-1 CM) decreased the susceptibility of tumor cells to NK cell cytotoxicity, as a result of increased programmed death receptor ligand 1 (PD-L1) and decreased NK group 2D (NKG2D) ligands in CRPC cells. Meanwhile, the decreased susceptibility of tumor cells was also detected when NK cells were treated with THP-1 CM and used in NK cell cytotoxicity tests. Therefore, we observed higher resistance of CRPC cells when both tumor and NK cells were treated with THP-1 CM than when tumor cells or NK cells were individually treated. We further discovered that the PMA/IL-4 treated THP-1 cells secrete a high level of IL-6, so blocking the IL-6 action significantly decreased the PD-L1 level while recovering the NKG2D ligands, thus increasing the susceptibility of CRPC cells to NK cell action. Moreover, we discovered that JAK-Stat3 is the most critical IL-6 downstream signaling in triggering the THP-1 CM effect. Consequently, we found the susceptibility of CRPC cells to NK cells was increased when either JAK or Stat 3 inhibitor was added when tumor cells were treated with THP-1 CM, and that the best effect was observed when the JAK inhibitor and PD-L1 Ab were added together.
- Subjects :
- Cytotoxicity, Immunologic
Male
0301 basic medicine
Cell
In Vitro Techniques
Biology
B7-H1 Antigen
03 medical and health sciences
0302 clinical medicine
Cell Movement
PD-L1
Tumor Cells, Cultured
medicine
Humans
Cytotoxic T cell
Secretion
Receptor
Interleukin 6
Cell Proliferation
Macrophages
Prostatic Neoplasms
Cell Differentiation
Cell Biology
NKG2D
In vitro
Killer Cells, Natural
030104 developmental biology
medicine.anatomical_structure
Drug Resistance, Neoplasm
Culture Media, Conditioned
030220 oncology & carcinogenesis
Cancer research
biology.protein
Signal Transduction
Subjects
Details
- ISSN :
- 00144827
- Volume :
- 364
- Database :
- OpenAIRE
- Journal :
- Experimental Cell Research
- Accession number :
- edsair.doi.dedup.....d2ffc7713f49e034269a97cb34978be1