Primary T Cells from Cutaneous T-cell Lymphoma Skin Explants Display an Exhausted Immune Checkpoint Profile

Cancer Immunol Res. 2018 Aug;6(8):900-909. doi: 10.1158/2326-6066.CIR-17-0270. Epub 2018 Jun 12.


Cutaneous T-cell lymphoma (CTCL) develops from clonally expanded CD4+ T 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 émigrés from epidermal and dermal explant cultures of skin biopsies from CTCL patients (n = 37) and healthy donors (n = 5). Compared with healthy skin, CD4+ CTCL populations contained more T cells expressing PD-1, CTLA-4, and LAG-3. CD8+ CTCL 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 émigrés 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 CD4+ and CD8+ T 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. Cancer Immunol Res; 6(8); 900-9. ©2018 AACR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / analysis
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Dendritic Cells / immunology
  • Epidermis / immunology
  • Female
  • Gene Expression Profiling / methods
  • Genes, cdc / genetics
  • Humans
  • Immunophenotyping
  • Lymphocyte Activation / immunology
  • Lymphoma, T-Cell, Cutaneous / genetics
  • Lymphoma, T-Cell, Cutaneous / immunology*
  • Lymphoma, T-Cell, Cutaneous / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Skin Neoplasms / genetics
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / pathology
  • Tumor Cells, Cultured
  • Young Adult


  • B7-H1 Antigen
  • CD274 protein, human
  • RNA, Messenger
  • RNA, Neoplasm