Primary t cells from cutaneous t-cell lymphoma skin explants display an exhausted immune checkpoint profile Academic Article uri icon


MeSH Major

  • Models, Statistical
  • Mycosis Fungoides
  • Sezary Syndrome
  • Skin Neoplasms


  • © 2018 American Association for Cancer Research. Cutaneous T-cell lymphoma (CTCL) develops from clonally expanded CD4þT cells in a background of chronic inflammation. Although dendritic cells (DCs) stimulate T cells and are present in skin, cutaneous T cells in CTCL do not respond with effective antitumor immunity. We evaluated primary T-cell and DC emigres from epidermal and dermal explant cultures of skin biopsies from CTCL patients (n ¼ 37) and healthy donors (n ¼ 5). Compared with healthy skin, CD4þCTCL populations contained more T cells expressing PD-1, CTLA-4, and LAG-3. CD8þCTCL populations contained more T cells expressing CTLA-4 and LAG-3. CTCL populations also contained more T cells expressing the inducible T-cell costimulator (ICOS), a marker of T-cell activation. DC emigres from healthy or CTCL skin biopsies expressed PD-L1, indicating that maturation during migration resulted in PD-L1 expression irrespective of disease. Most T cells did not express PD-L1. Using skin samples from 49 additional CTCL patients for an unsupervised analysis of genome-wide mRNA expression profiles corroborated that advanced T3/T4-stage samples expressed more checkpoint inhibition mRNA compared with T1/T2 stage patients or healthy controls. Exhaustion of activated T cells is therefore a hallmark of both CD4þand CD8þT cells isolated from the lesional skin of patients with CTCL, with increasing expression as the disease progresses. These results justify identification of antigens driving T-cell exhaustion and the evaluation of immune checkpoint inhibition to reverse T-cell exhaustion earlier in the treatment of CTCL

publication date

  • August 2018



  • Academic Article



  • eng

PubMed Central ID

  • PMC6074045

Digital Object Identifier (DOI)

  • 10.1158/2326-6066.CIR-17-0270

PubMed ID

  • 29895574

Additional Document Info

start page

  • 900

end page

  • 909


  • 6


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