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

Cancer Letters
Bongkum ChoiKi-Young Lee

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 inclu...Continue Reading

Citations

Mar 9, 2021·Frontiers in Immunology·Isabelle SerrCarolin Daniel
Mar 13, 2021·Advanced Drug Delivery Reviews·Carina PeresHelena F Florindo
Apr 12, 2021·Biotechnology and Applied Biochemistry·Seyyed Hossein KhatamiAhmad Movahedpour
Jul 3, 2021·Journal of Personalized Medicine·Md Abdus SubhanVladimir P Torchilin
Aug 10, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Fan TangXia-Wei Wei

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