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. 2015:2015:761378.
doi: 10.1155/2015/761378. Epub 2015 Apr 14.

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

Mara Giavina-Bianchi  1 , Pedro Giavina-Bianchi  2 , Mirian Nacagami Sotto  1 , Alona Muzikansky  3 , Jorge Kalil  2 , Cyro Festa-Neto  1 , Lyn M Duncan  4
Affiliations

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

Mara Giavina-Bianchi et al. J Immunol Res. 2015.

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.

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Figures

Figure 1
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
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
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
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
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.
See this image and copyright information in PMC

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