TY - JOUR
T1 - The host protecting the tumor from the host — targeting PD‑L1 expressed by host cells
AU - Munn, David H.
N1 - Funding Information:
DHM is supported by NIH R01 CA103320 and CA21229.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - Tumors frequently escape from immune surveillance by hijacking the natural control mechanisms that regulate normal immune responses. The programmed death‑1 receptor (PD‑1) on T cells normally helps limit excessive immune activation, but it can also suppress beneficial antitumor immunity. In the clinic, blocking either PD‑1 or one of its principal counterligands, programmed death–ligand 1 (PD‑L1), can lead to dramatic responses in certain patients. Because PD‑L1 can be expressed by both the tumor cells themselves and also the host cells, including host immune cells, the actual mechanistic target of therapy has remained unclear. In the current issue of the JCI, two papers, one by Tang and colleagues and the other by Lin and colleagues, used a variety of mouse tumor models to demonstrate that the relevant target for therapy in each case was the PD‑L1 molecules expressed by host cells and not by tumor cells. If this finding is generalized to humans, then it would suggest that the tumor persuades the host to actively suppress its own attempted immune response against the tumor cells.
AB - Tumors frequently escape from immune surveillance by hijacking the natural control mechanisms that regulate normal immune responses. The programmed death‑1 receptor (PD‑1) on T cells normally helps limit excessive immune activation, but it can also suppress beneficial antitumor immunity. In the clinic, blocking either PD‑1 or one of its principal counterligands, programmed death–ligand 1 (PD‑L1), can lead to dramatic responses in certain patients. Because PD‑L1 can be expressed by both the tumor cells themselves and also the host cells, including host immune cells, the actual mechanistic target of therapy has remained unclear. In the current issue of the JCI, two papers, one by Tang and colleagues and the other by Lin and colleagues, used a variety of mouse tumor models to demonstrate that the relevant target for therapy in each case was the PD‑L1 molecules expressed by host cells and not by tumor cells. If this finding is generalized to humans, then it would suggest that the tumor persuades the host to actively suppress its own attempted immune response against the tumor cells.
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U2 - 10.1172/JCI99047
DO - 10.1172/JCI99047
M3 - Review article
C2 - 29337304
AN - SCOPUS:85041465178
SN - 0021-9738
VL - 128
SP - 570
EP - 572
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 2
ER -