Mobilizing phospholipids on tumor plasma membrane implicates phosphatidylserine externalization blockade for cancer immunotherapy
Weihong Wang, Shaoxian Wu, Zhanpeng Cen, Yixin Zhang, Yuang Chen, Yixian Huang, Anthony R. Cillo, J Prokopec, Giovanni Quarato, Dario A.A. Vignali, Jacob Stewart-Ornstein, Song Li, Binfeng Lu, Yi‐Nan Gong
Abstract
, with tumor cells lacking the PS scramblase Xkr8 and unable to expose PS during otherwise normal apoptosis, we find that the accumulated apoptotic tumor cells produce and release cyclic GAMP (cGAMP) to immune cells to activate the STING pathway, leading to TAM M1 polarization, suppressed interleukin (IL)-10 secretion, and natural killer (NK) cell cytotoxicity. Silencing Xkr8 in vivo by either short hairpin RNA (shRNA) or small interfering RNA (siRNA) to achieve a PS externalization blockade provides robust therapeutic anti-tumor efficiency.