Original ArticlesDecline in MHC class I expression with increasing thickness of cutaneous melanomas in standard-strain transgenic mouse modelsMilling, S. W. F.; Silvers, W. K.; Sai, T.; Mintz, B.*Author Information Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA, USA. Tel: (+1) 215 728 2479; Fax: (+1) 215 728 3574. (Received 23 July 2001;accepted in revised form 20 September 2001) *To whom correspondence should be addressed Melanoma Research: June 2002 - Volume 12 - Issue 3 - p 221-230 Buy Abstract Major histocompatibility complex (MHC) class I proteins are required for the formation of complexes with antigenic peptides that enable cytotoxic T lymphocytes (CTLs) to recognize and lyse target cells. The frequent loss of MHC class I expression reported in human melanomas and melanoma cell lines may therefore be an obstacle to CTL-based immunotherapy. We have investigated the expression of MHC class I proteins in the cutaneous melanomas of Tyr-SV40E (C57BL/6 strain) transgenic mice in order to evaluate their potential as experimental models for immunotherapy. The SV40 large T (LT) oncoprotein, which is expressed exclusively in the melanocytic lineages of these mice, was used as a marker for flow cytometric analysis of the parenchymal (potential target) cells of 35 freshly dissociated samples from 28 primary tumours. All the tumours were ulcerated and exceeded the Breslow thickness indicative of a poor clinical prognosis in human melanoma. Using antibodies against H-2Db and H-2Kb class I proteins, the LT antigen-positive cells were found to have high levels of both these MHC class I molecules in the thinnest tumours (2 mm), whereas the levels tended to decline with increasing tumour thickness. Among the tumours > 4 mm thick, five had no detectable MHC class I expression. Unexpectedly, the apparent loss of H-2Db and H-2Kb proteins was observed not only in LT-positive cells but also in LT-negative cell populations. Expression of both H-2Db and H-2Kb was restored in tumours derived from a class I-low melanoma cell line by treatment of the hosts with interferon-γ. These results implicate a regulatory defect as a principal cause of the loss of MHC class I antigens, as noted by others in some human tumours, and they demonstrate that this loss is remediable, even in advanced stages of melanomas. © 2002 Lippincott Williams & Wilkins, Inc.