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Immune Checkpoint Blockade in Cancer Immunotherapy: Mechanisms, Clinical Outcomes, and Safety Profiles of PD-1/PD-L1 Inhibitors

  • Review
  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Programmed cell death protein 1 (PD-1) and its ligand PD-L1 are critical for the regulation of T cell exhaustion and activity suppression. Tumor cells expressing immune checkpoints including PD-L1 escape monitoring of T cells from the host immune system. Checkpoint inhibitors are highly promising therapies that function as tumor-suppressing factors via modulation of tumor cell–immune cell interactions as well as boosting T cell-mediated anti-tumor immunity. Notably, PD-1 or PD-L1 monoclonal antibody (mAb) has demonstrated promising therapeutic effects in clinical studies of many types of cancer. These mAbs have caused significant tumor regression with impressive anti-tumor response rates as well as a favorable safety profile in cancer patients. Furthermore, the combination of PD-1/PD-L1 mAbs with other types of anti-tumor agents has also developed to boost the anti-tumor responses and enhance therapeutic effects in cancer patients. This review clarifies the mechanisms of PD-1/PD-L1-mediated anti-cancer immune responses and some clinical studies of mAbs targeting PD-1/PD-L1. The challenges and future of PD-1/PD-L1 blockade therapy are also discussed.

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Data Availability

All of the data analyzed in this study were included in the final published article.

Abbreviations

PD-1:

Programmed cell death protein 1

PD-L1:

Programmed death ligand 1

mAbs:

Monoclonal antibodies

Tregs:

Regulatory T cells

APCs:

Antigen-presenting cells

CTLA-4:

Cytotoxic T-lymphocyte protein 4

NSCLC:

Non-small cell lung cancer

IFN-γ:

Interferon-γ

TNF-α:

Tumor necrosis factor-α

IL-2:

Interleukin-2

DC:

Dendritic cells

NK:

Natural killer

SHP-2:

Src homology 2

PI3K:

Phosphatidylinositol 3-kinase

MHC:

Major histocompatibility complex

CRC:

Colorectal cancer

CRPC:

Castrate-resistant prostate cancer

RCC:

Renal cell cancer

ORR:

Objective response rate

BRAF:

Proto-oncogene B-Raf

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Funding

This work was supported by the Social Development of Science and Technology Bureau of Zhangjiagang City (Grant No. ZKS1734) and Project of Diagnosis and Treatment Technology for Key Clinical Diseases of Suzhou (Grant No. LCZX201617).

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Author notes

  1. Yan Yan, Li Zhang and Yun Zuo contributed equally to this work.

Authors and Affiliations

  1. The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, 215600, Jiangsu, People’s Republic of China

    Yan Yan, Yun Zuo & Heya Qian

  2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People’s Republic of China

    Li Zhang

  3. College of Pharmacy, University of South Carolina, Columbia, SC, 29208, USA

    Li Zhang

  4. College of Pharmacy, University of Rhode Island, Kingston, RI, 02881, USA

    Chang Liu

Authors
  1. Yan Yan
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  2. Li Zhang
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  3. Yun Zuo
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  4. Heya Qian
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  5. Chang Liu
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Contributions

YY, LZ, YZ, and HQ wrote the manuscript. CL contributed to the English assessment and manuscript revision. All of the authors read and approved the final manuscript.

Corresponding authors

Correspondence to Li Zhang or Chang Liu.

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Yan, Y., Zhang, L., Zuo, Y. et al. Immune Checkpoint Blockade in Cancer Immunotherapy: Mechanisms, Clinical Outcomes, and Safety Profiles of PD-1/PD-L1 Inhibitors. Arch. Immunol. Ther. Exp. 68, 36 (2020). https://doi.org/10.1007/s00005-020-00601-6

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  • DOI: https://doi.org/10.1007/s00005-020-00601-6

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