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Cutaneous T cell lymphoma cells are targets for immune checkpoint ligand PD-L1-specific, cytotoxic T cells

Leukemia volume 27, pages 2251–2253 (2013)Cite this article

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Cutaneous T cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin's lymphoma, characterized by the appearance of malignant T cells in the skin and—in most cases—by an indolent course of disease. The immunogenicity of CTCL has been demonstrated by therapeutic modulation of the immune system, which resulted in objective remissions and control of disease.1 Unfortunately, however, CTCL patients, particularly in advanced stages or suffering from more aggressive forms, develop severe immunodeficiency.2

Different mechanisms contribute to the inhibition of cellular immunity, for example, constitutive activation of the Jak/Stat pathway, loss of the T cell receptor repertoire complexity, deregulated expression of immunosuppressive cytokines and immune regulatory proteins such as CTLA-4, FasL and programmed cell death protein 1 (PD-1) ligands, that is, PD-L1 and PD-L2.2 The major role of the PD-1 pathway is not at the initial T cell activation stage, but rather to regulate effector T cell responses in tissues by downregulating the activity of T cells in order to limit collateral tissue damage.3 Accordingly, PD-1+ tumor-infiltrating lymphocytes are inhibited by PD-L1 expressed by cancerous cells or other cells in the tumor microenvironment. In two recent clinical trials, antibody-mediated blockade of either PD-1 or PD-L1 resulted in outstanding clinical responses.4, 5 Remarkably, an association between response and PD-L1 expression on tumor cells was observed.

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Authors and Affiliations

  1. Department of Hematology, Center for Cancer Immune Therapy (CCIT), Copenhagen University Hospital, Herlev, Denmark

    S Munir, G H Andersen & M H Andersen

  2. Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark

    A Woetmann & N Ødum

  3. Department of General Dermatology, Medical University of Graz, Graz, Austria

    J C Becker

Authors
  1. S Munir
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  2. G H Andersen
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  6. M H Andersen
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Correspondence to M H Andersen.

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Competing interests

The corresponding author has previously filed a patent application based on the use of PD-L1 for vaccination. The rights of the patent application have been transferred to Herlev Hospital through the Capital Region of Denmark. The remaining authors declare no conflict of interest.

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Munir, S., Andersen, G., Woetmann, A. et al. Cutaneous T cell lymphoma cells are targets for immune checkpoint ligand PD-L1-specific, cytotoxic T cells. Leukemia 27, 2251–2253 (2013). https://doi.org/10.1038/leu.2013.118

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