While it is generally accepted that host cellular immunity plays a critical role in regulating melanoma progression in situ, the early phases of melanocytic tumorigenesis and of anti-tumor immune reactivity remain poorly described. Lymphoid (CD4+ and CD8+ T) and myeloid (macrophage and dendritic) cells are regularly observed in nevi exhibiting atypia and in radial growth phase (RGP) lesions, but less apparent in vertical growth phase (VGP) lesions and metastatic melanoma. The presence of such infiltrates in premalignant melanocytic lesions has been correlated in certain instances with spontaneous regression of atypical cell clusters and with the vitiliginous auto-destruction of normal melanocytes. Despite evidence for specificity in the infiltrating immune response, little data exists to fully characterize the cellular immune response to such premalignant lesions. We have recently noted that many atypical, but not normal benign, nevi express the melanoma-associated antigen MAGE-1 and are infiltrated with CD45RO+ perforin+ effector T cells. We hypothesize that the localization of mature effector T cells in regions of atypical nevi expressing tumor-associated antigens supports the locoregional activation of specific T cells. In addition, we and others have noted lesional infiltration by dendritic cells. The number and functional status of dendritic cells (DC) in melanoma lesions has been previously associated with either tumor progression or with tumor regression, low metastatic potential, and long-term patient survival. A systematic evaluation of DCs in atypical nevi (AN) will provide insight into the the impact of immune cells on the development of melanoma from preneoplastic lesions. We propose to characterize the T cell and antigen presenting cells present in untreated AN and AN resected from patients undergoing IFN-a therapy, and to correlate this with the degree of atypia and expression of neo-antigens. We anticipate that the results of these studies will provide us with an immunologic basis for understanding disease progression or therapy induced-regression.
| Wankowicz-Kalinska, Anna; Mailliard, Robbie B; Olson, Kathleen et al. (2006) Accumulation of low-avidity anti-melanocortin receptor 1 (anti-MC1R) CD8+ T cells in the lesional skin of a patient with melanoma-related depigmentation. Melanoma Res 16:165-74 |
| Wankowicz-Kalinska, Anna; Le Poole, Caroline; van den Wijngaard, Rene et al. (2003) Melanocyte-specific immune response in melanoma and vitiligo: two faces of the same coin? Pigment Cell Res 16:254-60 |
| Tatsumi, Tomohide; Kierstead, Lisa S; Ranieri, Elena et al. (2002) Disease-associated bias in T helper type 1 (Th1)/Th2 CD4(+) T cell responses against MAGE-6 in HLA-DRB10401(+) patients with renal cell carcinoma or melanoma. J Exp Med 196:619-28 |
