br Programmed death ligand PD L also known as
Programmed death-ligand 1 (PD-L1, also known as CD274 and B7-H1) is a critical “don't find me” signal to the adaptive immune system. Upregulation of PD-L1 is another strategy for tumor ASP1517 to evade the immune system. The suppression of PD-L1 to elicit an immune response against tumors has been translated to the clinic with very encouraging results. Here, our findings indicated that PD-L1 was dominantly ex-pressed on CD90hi PDAC cells, a mechanism by which these “stem-like” cells avoid an adaptive immune response. As we have shown, CD90 could be regulated by Sonic Hedgehog and Hippo-YAP signaling. These two pathways have been reported to be associated with PD-L1 expres-sion levels in tumors, which may explain the coexistence of PD-L1 and CD90 on PDAC cells.
Taken together, CD90hi “stem-like” cells created an im-munosuppressive niche through reprogramming monocytes/macro-phages and suppressing antitumor T cells directly, which favored the progression of pancreatic cancer. Elucidation of the crosstalk between immune cells and PDAC cells, especially pancreatic CSCs, would foster a better understanding of pancreatic cancer progression and provide a potential therapeutic strategy for targeting PDAC.
Conflicts of interest
All authors have declared that no conflict of interest exists.
This work was supported by Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning No. TP2015007 (J. Xue), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support No. 20161312 (J. Xue), and the National Natural Science Foundation of China Nos. 81702938 and. 81770628 (J. Xue).
JJ.S. and J.X. designed the experiment, interpreted the data and wrote the manuscript; JJ.S. performed most of the experiments; P.L. and WY.S. assisted in some experiments; RZ.H. and MW.Y., under the supervision of YW.S., collected tissues from pancreatic cancer patients and organized their clinical information; T.F. assisted in some discus-sion; J.X., NN.N. and YW.S. provided an overall guide.
Appendix A. Supplementary data
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