%0 Journal Article
%T Immune profiling of microsatellite instability-high and polymerase ¦Å ( POLE )-mutated metastatic colorectal tumors identifies predictors of response to anti-PD-1 therapy
%A Chongkai Wang
%A Jun Gong
%A Marwan Fakih
%A Peter P. Lee
%A Travis Y. Tu
%J SCIE-indexed Journal
%D 2018
%X Early evidence supporting the concept of programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) blockade as a form of cancer immunotherapy arose from preclinical studies demonstrating that activation of the PD-1/PD-L1 axis suppressed the activation and proliferation of tumor antigen-specific T cells and promoted tumorigenesis, which was reversed with PD-1/PD-L1 blockade (1,2). Initial phase I studies investigating several humanized monoclonal IgG4 antibodies targeting PD-1 and PD-L1 in advanced solid tumors were soon conducted and paved way for the development of the first PD-1 inhibitors, nivolumab and pembrolizumab, approved by the Food and Drug Administration (FDA) (3-5). In the studies that have followed, PD-L1 expression [most often ¡Ý1% or ¡Ý5% by immunohistochemistry (IHC)] was among the first candidate predictors of response to PD-1 blockade and has been associated with a 20¨C50% response rate to PD-1 inhibitors in select solid tumors (5-7). However, the documentation of PD-L1-negative patients with a response to anti-PD-1 therapy argues against the use of PD-L1 expression as the sole biomarker for selection (6)
%U http://jgo.amegroups.com/article/view/18735/html