Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma.
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.
Hino
Ryosuke
R
Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan. hinoti@med.uoeh-u.ac.jp
Kabashima
Kenji
K
Kato
Yu
Y
Yagi
Hiroaki
H
Nakamura
Motonobu
M
Honjo
Tasuku
T
Okazaki
Taku
T
Tokura
Yoshiki
Y
D000368:Aged; D015703:Antigens, CD / Q000032:analysis*; D051017:Apoptosis Regulatory Proteins / Q000032:analysis*; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000139:chemically induced / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor