PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy
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TLDR
Improved understanding of the host immune system and tumor microenvironment will better elucidate which patients derive benefit from these promising agents, and the issue of PD-L1 as an exclusionary predictive biomarker is clarified.Abstract:
The resurgence of cancer immunotherapy stems from an improved understanding of the tumor microenvironment. The PD-1/PD-L1 axis is of particular interest, in light of promising data demonstrating a restoration of host immunity against tumors, with the prospect of durable remissions. Indeed, remarkable clinical responses have been seen in several different malignancies including, but not limited to, melanoma, lung, kidney, and bladder cancers. Even so, determining which patients derive benefit from PD-1/PD-L1-directed immunotherapy remains an important clinical question, particularly in light of the autoimmune toxicity of these agents. The use of PD-L1 (B7-H1) immunohistochemistry (IHC) as a predictive biomarker is confounded by multiple unresolved issues: variable detection antibodies, differing IHC cutoffs, tissue preparation, processing variability, primary versus metastatic biopsies, oncogenic versus induced PD-L1 expression, and staining of tumor versus immune cells. Emerging data suggest that patients whose tumors overexpress PD-L1 by IHC have improved clinical outcomes with anti-PD-1-directed therapy, but the presence of robust responses in some patients with low levels of expression of these markers complicates the issue of PD-L1 as an exclusionary predictive biomarker. An improved understanding of the host immune system and tumor microenvironment will better elucidate which patients derive benefit from these promising agents.read more
Citations
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Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers.
Aaron M. Goodman,Shumei Kato,Lyudmila Bazhenova,Sandip Pravin Patel,Garrett M. Frampton,Vincent A. Miller,Philip J. Stephens,Gregory A. Daniels,Razelle Kurzrock +8 more
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Exosomal PD-L1 Contributes to Immunosuppression and is Associated with anti-PD-1 Response
Chen Gang,Alexander C. Huang,Wei Zhang,Wei Zhang,Gao Zhang,Wu Min,Wei Xu,Zi-Li Yu,Jiegang Yang,Jiegang Yang,Beike Wang,Beike Wang,Honghong Sun,Hou-Fu Xia,Qiwen Man,Wenqun Zhong,Wenqun Zhong,Leonardo F. Antelo,Bin Wu,Xuepeng Xiong,Xiaoming Liu,Lei Guan,Lei Guan,Ting Li,Ting Li,Shujing Liu,Ruifeng Yang,Youtao Lu,Liyun Dong,Suzanne McGettigan,Rajasekharan Somasundaram,Ravi Radhakrishnan,Gordon B. Mills,Yiling Lu,Junhyong Kim,Youhai H. Chen,Haidong Dong,Yi-Fang Zhao,Giorgos C. Karakousis,Tara C. Mitchell,Lynn M. Schuchter,Meenhard Herlyn,E. John Wherry,Xiaowei Xu,Wei Guo +44 more
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Immune checkpoint inhibitors: recent progress and potential biomarkers.
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Predictive biomarkers for checkpoint inhibitor-based immunotherapy.
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