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Cancer Lett. 2020 May 28;478:56-69. doi: 10.1016/j.canlet.2020.02.042. Epub 2020 Mar 4.

Anti-tumor effects of anti-PD-1 antibody, pembrolizumab, in humanized NSG PDX mice xenografted with dedifferentiated liposarcoma.

Author information

1
Department of Medicine, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea; GenNBio, Inc., Seoul, Republic of Korea.
2
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
3
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea. Electronic address: jbparkmd@gmail.com.
4
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea. Electronic address: thylee@skku.edu.

Abstract

The efficacy of an immune checkpoint blockade has been demonstrated against various types of cancer, but its suitability has not been fully proven for therapies specifically targeting sarcoma. We conducted a pan-cancer tumor data analysis to identify key immune-related variables strongly associated with sarcoma prognosis, and we explored whether these expected factors are functionally correlated with anti-PD-1 therapy in humanized (Hu) NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice xenografted with dedifferentiated liposarcoma (DDLPS). We found that an abundance of hCD8+ T cells and hNK cells was functionally associated with anti-PD-1 effects in the Hu-NSG DDLPS mice. Phenotypically, these cells were shown to be hCD8+IFNγ+, hCD8+PD-1+, hCD8+Ki-67+, hCD56+IFNγ+, hCD56+PD-1+, and hCD56+Ki-67+ cells and were enriched in splenocytes and tumor-infiltrating lymphocytes (TILs) of Hu-NSG DDLPS mice treated with anti-PD-1 antibody. Moreover, a considerable increase in activated hCD56+NKp46+NKG2D+ NK cells was also detected. Our findings suggest that hCD8+ T and hNK subsets play a pivotal role in anti-DDLPS tumor effects of anti-PD-1 therapy. The results provide clinical reference for advanced anti-PD-1 therapy targeting sarcoma tumors including DDLPS.

KEYWORDS:

Anti-PD-1 antibody; Dedifferentiated liposarcoma; Humanized mouse model; Immunotherapy; Patient-derived xenograft

Conflict of interest statement

Declaration of competing interest The authors declare no potential conflicts of interest.

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