A natural killer–dendritic cell axis defines checkpoint therapy responsive tumor microenvironments (Nature Medicine 2018, 24:1178–1191)

報告日期: 2018/11/02
報告時間: 15:10/16:00
報告學生: 李忠諺
講評老師: 張志鵬
附件下載: 下載[1750-1538016306-1.pdf] 

A natural killer–dendritic cell axis defines checkpoint therapy–responsive tumor microenvironments

Kevin C. Barry, Joy Hsu, Miranda L. Broz, and Matthew F. Krummel

Nature medicine (2018)

Presenter: Chung-Yen Li

Coordinator: Prof. Chia-Yih Wang              Date/Time: 2018/11/02 15:10-16:00

Commentator: Prof Chih-Peng Chang.        Location: Room 602, Med. College Building

Abstract

Anti–programmed cell death protein 1 (PD-1) immunotherapy had been exceedingly effective in activating T cell responses to cancer. However, only 20% of patients had a response to this treatment [1]. Indicating that had other mechanism, immune parameters and cell types were involved in. Authors previously found a rare stimulatory dendritic cells (SDC) which re-stimulated the T cells within the tumor microenvironment (TME). In this study, the authors found that the high levels of BDCA-3+ SDCs in the TME correlated with better outcomes of patients with melanoma. In addition, the cytokine Fms-related tyrosine kinase 3 ligand (FLT3LG) expression levels in the TME correlated with intratumoral SDCs levels and better overall survival (OS). Flt3l reporter mouse model demonstrated that the expression FLT3LG of TME was from intratumoral natural killer (NK) cells. Furthermore, intratumoral NK cells controlled the levels of SDCs in TME and NK cells also correlated with the levels of SDCs in the human melanoma and the responsiveness to anti-PD1 immunotherapy. These findings suggest that NK cells, which expressed the FLT3LGin tumor, regulated the levels of intratumoral SDCs and enhanced the responsiveness of patients to anti-PD-1 immunotherapy.

  1. Topalian, S.L., C.G. Drake, and D.M. Pardoll, Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell, 2015. 27(4): p. 450-61.