Activated and expanded natural killer cells target osteosarcoma tumor initiating cells in an NKG2D-NKG2DL dependent manner. Cancer Lett. 2015 Nov 1;368(1):54-63. doi: 10.1016/j.canlet.2015.07.042. Epub 2015 Aug 11

報告日期: 2015/11/13
報告時間: 5:10/6:00
報告學生: 翁閎楷
講評老師: 鄭宏祺
附件下載: 下載[1521-1443055028-1.pdf] 

Activated and expanded natural killer cells target osteosarcoma tumor initiating cells in an NKG2D-NKG2DL dependent manner

L. Fernández, J. Valentín, M. Zalacain, W. Leung, A. Patiño-García, A. Pérez-Martínez

Cancer Lett. 2015 Nov 1;368(1):54-63. doi: 10.1016/j.canlet.2015.07.042

Speaker: Hung-Kai Weng (翁閎楷)

Commentator: Prof. Hung-Chi Cheng (鄭宏祺老師)

Time: 17:10-18:00, Nov. 13th, 2015 (Fri.)

Place: Room 602

Abstract:

  Osteosarcoma (OS) is the most common primary malignant bone tumor, mainly affecting children and adolescents. OS usually occurs at long bone, particularly around the knee, including distal femur and proximal tibia. For the past three decades, the survival of patients with osteosarcoma was improved, but not so much. Till now, the mainstream treatments are still only surgical excision combined with neoadjuvant and adjuvant chemotherapy, which could let 5-year survival rate reach around 70%. However, 5-year survival rate dropped to only 20-25% in patients with metastatic disease and 50% in poor response to chemotherapy. Recent clinical trials of targeted agents have been generally disappointing. Therefore, the research trends are toward immune-targeted therapies. The authors explored the efficacy and the pathways involved in natural killer (NK) cells’ elimination of OS cells, including tumor initiating cells (TICs), which are responsible for chemotherapy resistance, recurrence, and metastasis. The expression of ligands for NK cell receptors was studied in primary OS cell lines by flow cytometry. In vitro cytotoxicity of activated and expanded NK (NKAE) cells against OS was tested, and this cytolytic activity relied on interaction between NKG2D receptor and NKG2D ligands. Spironolactone (SPIR) was also tested, and it could increase OS cells’ susceptibility to lysis by NKAE cells, and could shrink the OS TICs in vitro and in vivo. The results show NKAE cells target OS cells including the TICs compartment, supporting the use of NK-cell based immunotherapies for OS.

Reference:

  1. Kansara M, Teng MW, Smyth MJ, Thomas DM. Translational biology of osteosarcoma. Nat Rev Cancer 2014;14:722-35.
  2. Hung GY, Yen HJ, Yen CC, et al. Experience of pediatric osteosarcoma of the extremity at a single institution in Taiwan: prognostic factors and impact on survival. Ann Surg Oncol 2015;22:1080-7.