In vitro-induced M2 type macrophages induces the resistance of prostate cancer cells to cytotoxic action of NK cells
Authors: Peter C Keng
Xiaodong Chen
Mingjing Shen
Ying Tsai
Lijun Xu
Dong-Rong Yang
Yuhchyau Chen
Soo Ok Lee
Journal: Experimental cell research (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CRPC; IL-6; Macrophages; NK cell cytotoxicity; NKG2D
Affiliations: Department of Radiation Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA; Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, PR China., Department of Radiation Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA., Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, PR China., Department of Radiation Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. Electronic address: .

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. 

Retracted: No

PubPeer comments:
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 Thank you for pointing our possible errors in the paper. I will review the raw data and find out what happened. These are likely errors in uploading images. Once confirmed, I will request a correction with Journal. Soo Ok Lee , 
 The previous comment was sent by Soo OK Lee, not by Peter C. Keng. , 
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 #4 Bands also overlap with *[at left]* Fig 5 of [Shen et al (2017)] ![file] To add to the existing overlaps with [Zhu et al (2018)] , [Xu et al (2018)] , [Chen et al (2019)] . Fig 5 of Shen et al. (2017) in turn links to **other** papers. ![] , 
 In the Erratum (Exp Cell Res. 2020 Apr 21:112006. doi: 10.1016 j.yexcr.2020.112006), p-JAK2 band in Fig 6A is still identical to p-ERK band in Fig 4A of Zhu et al (2018). ![file] ,