In vitro -induced M2 type macrophages induces the resistance of prostate cancer cells to cytotoxic action of NK cells
| Autor: | Dong-Rong Yang, Lijun Xu, Mingjing Shen, Xiaodong Chen, Peter C. Keng, Yuhchyau Chen, Ying Tsai, Soo Ok Lee |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | Experimental Cell Research. 364:113-123 |
| ISSN: | 0014-4827 |
| DOI: | 10.1016/j.yexcr.2018.01.041 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect