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2017 ; 9
(ä): 601-609
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Checkpoint blockade in solid tumors and B-cell malignancies, with special
consideration of the role of CD200
#MMPMID29180896
Gorczynski RM
; Zhu F
Cancer Manag Res
2017[]; 9
(ä): 601-609
PMID29180896
show ga
In the ontogeny of a normal immune response, a series of checkpoints must be
overcome to ensure that unwanted and/or harmful self-directed activation
responses are avoided. Many of the molecules now known to be active in this
overseeing of the evolving immune activation cascade, contributing inhibitory
signals to dampen an overexuberant response, belong to the immunoglobulin
supergene family. These include members of the CD28/CTLA-4:B7.1/B7.2
receptor/ligand family, PD-1 and PDL-1, CD200 and CD200R, and the more recently
described V-domain immunoglobulin suppressor of T-cell activation and its ligand
(VSIG-3/IGSF11). Unfortunately, from the point of view of improving
immunotargeting of cancer cells, triggering these checkpoint inhibitory signaling
pathways, so necessary to maintain self-tolerance, simultaneously acts to prevent
effective tumor immunity. The recent development of reagents, predominantly
antibodies, to act as checkpoint blockade agents, has had a dramatic effect on
human cancer treatment, with a marked reported success for anti-CTLA-4 and PD-1
in particular in clinical trials. This review provides a general overview of the
data now available showing the promise of such treatments to our cancer
armamentarium and elaborates in depth on the potential promise of what can be
regarded as an underappreciated target molecule for checkpoint blockade in
chronic lymphocytic leukemia and solid tumors, CD200.