On the biological relevance of MHC class II and B7 expression by tumour cells in melanoma metastases

Abstract

A large number of studies have indicated that specific immune reactivity plays a crucial role in the control of malignant melanoma. In this context, expression of MHC I, MHC II and B7 molecules by melanoma cells is seen as relevant for the immune response against the tumour. For a better understanding of the biological relevance of MHC II and B7 expression by tumour cells in metastatic melanoma, we studied the expression of these molecules in melanoma metastases in relation to the inflammatory response, regression of the tumour and survival from 27 patients treated with biochemotherapy (30 mg m À2 Cisplatin and 250 mg m À2 decarbazine (dimethyl-triazene-imidazole-carboxamide, DTIC) on days 1 -3 i.v., and 10 7 IU IFN-a2b 3 days a week s.c., q. 28d). In 19 out of 27 lesions studied, we found expression of MHC II by the tumour cells, while only in one out of 11 tumour biopsies obtained from untreated metastatic melanoma patients, MHC II expression was detected.

Phase I Study of the Intratumoral Administration of Recombinant Canarypox Viruses Expressing B7.1 and Interleukin 12 in Patients with Metastatic Melanoma

“…In a recent report, expression of B7.1 by tumor cells was found in 9 of 24 metastatic melanoma lesions. No significant correlation between B7.1 and tumor response to biochemotherapy, time to progression, or overall survival was found (28). The antitumor immune response by B7.1 and IL-12 in preclinical studies has been shown to be associated with a strong induction of IFN-g (18).…”

Low Surface Expression of B7-1 (CD80) Is an Immunoescape Mechanism of Colon Carcinoma

“…Importantly, CD80 and CD86 expression has been found in a series cases of human melanoma in which low levels of RNA expression have been frequently documented (40,41). These findings, precisely in a human malignancy characterized by a certain degree of intrinsic immunogenicity, suggest that B7 family molecules could be involved in subverting routes of immune destruction of tumors.…”

“…The expression of low levels of CD80 and CD86 has been detected on an important fraction of human melanomas (40,41), myelomas (42), and acute myeloid leukemias (43). Moreover, low levels of expression of CD80 and CD86 detected by RT-PCR and surface staining has been reported in a series of cell lines derived from human carcinomas including some of colorectal origin (44).…”

Melanosomal Targeting Sequences from gp100 Are Essential for MHC Class II–Restricted Endogenous Epitope Presentation and Mobilization to Endosomal Compartments

“…6A), the entire GFP sequence, from which the first methionine was changed for a valine, was cloned between the putative NH 2 -terminal signal sequence (residues [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and the last 70 residues from gp100 (residue 594 to the end). In pcDNA-gp/GFP+epit (presented in Fig.…”

“…Considering that f20% to 25% of melanomas naturally express MHC class II molecules during the process of malignant transformation (19), and perhaps >50% during inflammation and metastases formation (20,21), it is plausible that concomitant antigenic presentation by MHC class I and class II shapes antitumor responses mediating both positive and negative mechanisms. Thus, activation of tumor-specific CD8 + and CD4 + T cells may occur at the tumor site.…”