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

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Abstract
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, ≥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. © 2010 American Cancer Society.

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