PD-L2 Expression in Human Tumors: Relevance to Anti-PD-1 Therapy in Cancer

作者：Jennifer H. Yearley, Christopher J. Gibson, Ni Yu, Christina Moon, Erin Murphy, Jonathan Juco, Jared Lunceford, Jonathan D. Cheng, Laura Q.M. Chow, Tanguy Y. Seiwert, Masahisa Handa, Joanne E. Tomassini, Terrill K. McClanahan · 发表于：Clinical Cancer Research · 年份：2017 · DOI：10.1158/1078-0432.ccr-16-1761 · 被引用次数：606 · 研究领域：Cancer Immunotherapy and Biomarkers、Cancer Cells and Metastasis、CAR-T cell therapy research

Abstract Purpose: Tumor-associated PD-L1 expression is predictive of clinical response to PD-1–directed immunotherapy. However, PD-L1–negative patients may also respond to PD-1 checkpoint blockade, suggesting that other PD-1 ligands may be relevant to the clinical activity of these therapies. The prevalence of PD-L2, the other known ligand of PD-1, and its relationship to response to anti-PD-1 therapy were evaluated. Experimental Design: PD-L2 expression was assessed in archival tumor tissue from seven indications using a novel immunohistochemical assay. In addition, relationships between clinical response and PD-L2 status were evaluated in tumor tissues from patients with head and neck squamous cell carcinoma (HNSCC) with recurrent or metastatic disease, treated with pembrolizumab. Results: PD-L2 expression was observed in all tumor types and present in stromal, tumor, and endothelial cells. The prevalence and distribution of PD-L2 correlated significantly with PD-L1 (P = 0.0012–<0.0001); however, PD-L2 was detected in the absence of PD-L1 in some tumor types. Both PD-L1 and PD-L2 positivity significantly predicted clinical response to pembrolizumab on combined tumor, stromal and immune cells, with PD-L2 predictive independent of PD-L1. Response was greater in patients positive for both PD-L1 and PD-L2 (27.5%) than those positive only for PD-L1 (11.4%). PD-L2 status was also a significant predictor of progression-free survival (PFS) with pembrolizumab independent of P...