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PD-L1

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The PD-1/PD-L1 Pathway

Programmed death-ligand 1 (PD-L1), also known as CD274, is a ligand of PD-1. The ligation of PD-L1 to PD-1 leads to T-cell inhibition. PD-L1 is expressed in a multitude of tissues including muscles and nerves. Of relevance for cancer immunotherapy, PD-L1 can be expressed on the surface of tumor cells, tumor-associated macrophages (TAMs), and T lymphocytes and can subsequently inhibit PD-1-positive T cells. The expression of PD-L1 can be induced by cytokines such as IFNs, or alternatively PD-L1 can be expressed autonomously through aberrations in the EGFR signaling pathway.

PD1 limits the activation and function of potentially pathogenic self-reactive CD4+ and CD8+ T cells, and PD-L1 can shield target organs from autoimmune attack.

PD-L1 and PD-L2, another ligand of PD-1, are commonly expressed on the surface of dendritic cells or macrophages. PD-1 and PD-L1/PD-L2 belong to the family of immune checkpoint proteins that act as co-inhibitory factors that can halt or limit the development of the T cell response. The PD-1/PD-L1 interaction ensures that the immune system is activated only at the appropriate time in order to minimize the possibility of chronic autoimmune inflammation.

The Role of PD-1/PD-L1 in Cancer and Immunotherapy

Under normal conditions, the immune system performs a series of steps which lead to an anticancer immune response and cancer cell death, known as the cancer immunity cycle:

The PD-1/PD-L1 pathway represents an adaptive immune resistance mechanism that is exerted by tumor cells in response to endogenous immune anti-tumor activity. PD-L1 is commonly over expressed on tumor cells or on non-transformed cells in the tumor microenvironment. PD-L1 expressed on the tumor cells binds to PD-1 receptors on the activated T cells, which leads to the inhibition of the cytotoxic T cells. These deactivated T cells remain inhibited in the tumor microenvironment.

Monoclonal antibody therapies against PD-1 and PD-L1 are being routinely used including Nivolumab, an anti-PD-1 drug developed by Bristol-Myers Squibb, which is approved for previously treated metastatic melanoma and squamous non-small cell lung cancer; and Pembrolizumab, developed by Merck and approved for previously treated metastatic melanoma. There are several other immunotherapies associated with PD-1/PD-K1 under development.

The efficiency of the immune checkpoint blockade with monoclonal antibodies in cancer treatment is remarkable, but not all patients respond to a single therapy. To enhance and broaden the anti-tumor activity of immune checkpoint inhibition the next step is combining agents with synergistic mechanisms of action. An example of this is the success of the combination of PD-1/PD-L1 inhibition blockage with complementary checkpoint inhibitor CTLA-4 in melanoma and non-small cell lung cancer.

EUPROTEIN Offering

EUPROTEIN has developed and validated PD-1 and PD-L1 protein that could be potentially used in the discovery and development of new cancer immunotherapies. These high-quality proteins might also be applied in future development of diagnostic and progressive assays involved the PD-1/PD-L1 pathway.

Or if you need help expressing the PD-1 or PD-L1 protein or generating antibodies against them, please submit your inquiry by clicking the button below. Our service representative will get back to you promptly to discuss your project needs.

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Reference

  1. Sharpe A and Pauken K. The diverse functions of the PD1 inhibitory pathway. Nature Reviews Immunology (2017)
  2. Oncology Meets Immunology: The Cancer-Immunity Cycle. Chen D and Mellman I, Immunity (2013)
  3. The Blockade Of Immune Checkpoints In Cancer Immunotherapy. Pardoll D, Nature Reviews Cancer (2012)
  4. Combination immunotherapy: a road map. Ott, P. et al. Journal for ImmunoTherapy of Cancer (2017)