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Potential biomarker for checkpoint blockade immunotherapy and treatment strategy

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Tumor Biology

Abstract

Programmed cell death protein-1 (PD-1) and ligand (PD-L1) provide an important escape mechanism from immune attack, and blockade therapy of these proteins show promising clinical benefits in many types of cancer. PD-L1 can be induced by interferon-gamma (IFN-γ), hypoxia, or toll-like receptor (TLR)-mediated pathways that confer adaptive immune resistance, or upregulated by oncogenic signals leading to constitutive expression and resulting in intrinsic immune resistance. The PD-1/PD-L1 checkpoint blockade, which targets regulatory pathways in T cells to overcome immune resistance, is correlated to PD-L1 expression pattern and the presence of tumor-infiltrating lymphocytes (TILs). Meanwhile, immunogenic mutation loads show significant response to checkpoint blockade, which is probably due to PD-1/L1 status and TIL content. Finally, the clinical strategies to design effective checkpoint-targeting immunotherapies are based on the classification of inducible/constitutive expression of PD-L1 and the presence of TILs.

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Acknowledgments

This paper was supported by the Key Technologies Research and Development Program of Guangzhou (2011Y2-00014), the Key Laboratory Program of Guangdong (2012A061400006), and the Special Fund for Research in the Public Interest from the National Health and Family Planning Commission of the People’s Republic of China (grant 201402031).

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  1. Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, 106 Zhongshan Er Rd, Guangzhou, 510080, China

    Zhong-Yi Dong, Si-Pei Wu, Ri-Qiang Liao, Shu-Mei Huang & Yi-Long Wu

  2. Southern Medical University, Guangzhou, China

    Zhong-Yi Dong & Shu-Mei Huang

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Dong, ZY., Wu, SP., Liao, RQ. et al. Potential biomarker for checkpoint blockade immunotherapy and treatment strategy. Tumor Biol. 37, 4251–4261 (2016). https://doi.org/10.1007/s13277-016-4812-9

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