Immunotherapy for Cutaneous T-Cell Lymphoma: Current Landscape and Future Developments

J Cutan Med Surg. 2019 Sep/Oct;23(5):537-544. doi: 10.1177/1203475419867610. Epub 2019 Jul 29.

Abstract

Mycosis fungoides (MF) and Sézary syndrome (SS) are chronic, progressive primary cutaneous T-cell lymphomas (CTCLs) for which there are no curative treatments. Skin-directed therapies, such as phototherapy, radiation therapy, or topical nitrogen mustard, provide only short-term remissions. Numerous attempts with different chemotherapeutic regimes failed to achieve meaningful clinical responses. Immunotherapy seems to be a promising avenue to achieve long-term disease control in CTCL. There is compelling evidence indicating that MF and SS are immunogenic lymphomas, which can be recognized by the patient's immune system. However, CTCL uses different strategies to impair host's immunity, eg, via repolarizing the T-cell differentiation from type I to type II, recruiting immunosuppressive regulatory T-cells, and limiting the repertoire of lymphocytes in the circulation. Many currently used therapies, such as interferon-α, imiquimod, extracorporeal phototherapy, and allogeneic bone marrow transplant, seem to exert their therapeutic effect via activation of the antitumor cytotoxic response and reconstitution of the host's immune system. It is likely that novel immunotherapies such as immune checkpoint inhibitors, cancer vaccines, and chimeric antigen receptor-T cells will help to manage CTCL more efficiently. We also discuss how current genomic techniques, such as estimating the mutational load by whole genome sequencing and neoantigen calling, are likely to provide clinically useful information facilitating personalized immunotherapy of CTCL.

Keywords: Sézary syndrome; cutaneous T-cell lymphoma; immunogenicity; immunotherapy; mycosis fungoides.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Cancer Vaccines / therapeutic use
  • Humans
  • Immunotherapy*
  • Immunotherapy, Adoptive
  • Interferons / therapeutic use
  • Mycosis Fungoides / immunology
  • Mycosis Fungoides / therapy*
  • Nivolumab / therapeutic use
  • Photopheresis
  • Sezary Syndrome / immunology
  • Sezary Syndrome / therapy*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / therapy*

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • Cancer Vaccines
  • Nivolumab
  • Interferons
  • pembrolizumab