Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma

Cancer. 2010 Apr 1;116(7):1757-66. doi: 10.1002/cncr.24899.


Background: : Melanoma tends to be refractory to various immunotherapies because of tumor-induced immunosuppression. To investigate the mechanism underlining the immunosuppression of melanoma patients, the authors focused on programmed cell death-1 (PD-1)/PD-1 ligand 1 (PD-L1) interaction between tumor cells and T cells.

Methods: : Melanoma specimens were collected from 59 primary tumors, 16 lymph nodes, and 4 lesions of in-transit metastasis. Specimens stained with anti-PD-L1 monoclonal antibodies were digitalized to jpg files. To evaluate the intensity of PD-L1 expression, histograms were used, and the red density (RD) was measured. PD-1 expression on T cells was analyzed in blood samples from 10 patients who had stage IV melanoma and in 4 samples of in-transit metastases.

Results: : Twenty-five patients comprised the "low" PD-L1 expression group (RD value, <90), and 34 patients comprised the "high" group (RD value, > or =90). Breslow tumor thickness in the high-expression group was significantly higher than in the low-expression group. Univariate and multivariate analyses revealed that the overall survival rate of the high-expression group was significantly lower than that of the low-expression group. In all patients with stage IV disease who were examined, both CD8-positive and CD4-positive T cells had significantly higher PD-1 expression levels in the peripheral blood. Tumor-infiltrating T cells expressed high levels of PD-1, and its expression was elevated further during the clinical course.

Conclusions: : The current results indicated that there is a correlation between the degree of PD-L1 expression and the vertical growth of primary tumors in melanoma. Multivariate analysis demonstrated that PD-L1 expression is an independent prognostic factor for melanoma. Cancer 2010. (c) 2010 American Cancer Society.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD / analysis*
  • Apoptosis Regulatory Proteins / analysis*
  • B7-H1 Antigen
  • Biomarkers, Tumor / analysis*
  • Female
  • Humans
  • Male
  • Melanoma / chemically induced
  • Melanoma / metabolism*
  • Melanoma / mortality
  • Melanoma / pathology
  • Prognosis
  • Programmed Cell Death 1 Receptor
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • T-Lymphocytes / metabolism


  • Antigens, CD
  • Apoptosis Regulatory Proteins
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor