Increased NY-ESO-1 expression and reduced infiltrating CD3+ T cells in cutaneous melanoma

Abstract

NY-ESO-1 is a cancer-testis antigen aberrantly expressed in melanomas, which may serve as a robust and specific target in immunotherapy. NY-ESO-1 antigen expression, tumor features, and the immune profile of tumor infiltrating lymphocytes were assessed in primary cutaneous melanoma. NY-ESO-1 protein was detected in 20% of invasive melanomas (16/79), rarely in in situ melanoma (1/10) and not in benign nevi (0/20). Marked intratumoral heterogeneity of NY-ESO-1 protein expression was observed. NY-ESO-1 expression was associated with increased primary tumor thickness (P = 0.007) and inversely correlated with superficial spreading melanoma (P < 0.02). NY-ESO-1 expression was also associated with reduced numbers and density of CD3+ tumor infiltrating lymphocytes (P = 0.017). When NY-ESO-1 protein was expressed, CD3+ T cells were less diffusely infiltrating the tumor and were more often arranged in small clusters (P = 0.010) or as isolated cells (P = 0.002) than in large clusters of more than five lymphocytes. No correlation of NY-ESO-1 expression with gender, age, tumor site, ulceration, lymph node sentinel status, or survival was observed. NY-ESO-1 expression in melanoma was associated with tumor progression, including increased tumor thickness, and with reduced tumor infiltrating lymphocytes.

Figure 1

Immunohistochemical detection of NY-ESO-1 (+) tumor cells and CD3+, CD8+ FOXP3−, CD8−FOXP3+, and CD8+FOXP3+ infiltrating lymphocytes in primary cutaneous melanoma. (a) NY-ESO-1 regional expression, 3+ intensity (×400); (b) NY-ESO-1 complete expression, 3+ intensity (×200); (c) CD3+ lymphocyte (red, arrow) embracing a melanoma cell (×630); (d) CD8+FOXP3− lymphocytes (membranous purple staining), CD8−FOXP3+ lymphocytes (blue nuclear staining, arrowhead), and CD8+FOXP3+ cell (purple membranous and blue nuclear staining, arrow), ×400.

Figure 2

Association between primary cutaneous melanoma thickness and NY-ESO-1. Each point represents one patient, and the horizontal bars represent the mean melanoma thickness of each group (P = 0.007).

Figure 3

Tumor infiltrating lymphocytes (TIL) and NY-ESO-1 expression in primary cutaneous melanoma. NY-ESO-1 was associated with nonbrisk versus brisk and absent TIL (P = 0.07).

Figure 4

Number of CD3+, CD8+FOXP3−, CD8−FOXP3+, and CD8+FOXP3+ lymphocytes in NY-ESO-1 positive and negative primary cutaneous melanoma. Each geometric figure represents one patient. The horizontal bars represent the mean value.

Figure 5

Arrangement of CD3+ cells in TIL of NY-ESO-1 positive and negative primary cutaneous melanoma. Each geometric figure represents the percentage of cells in one patient. The horizontal bars represent the mean value.