Inflammatory cell infiltrates in human melanoma at different stages of tumor progression

Abstract

Progression of human melanoma is associated with changes in antigenic phenotypes of tumor cells. To establish whether inflammatory infiltrates in progressing melanoma also change, we studied 146 cutaneous melanomas at different stages of progression. Monoclonal antibodies (MAbs) against lymphocyte and macrophage subpopulations, interleukin-2 receptor (IL-2 R), immune interferon (IFN-gamma), and the IFN-gamma-inducible, progression-associated melanoma antigens HLA-DR and gp89 were applied in situ. During the course of melanoma progression, decreased amounts of peritumoral T cells, IL-2 R-expressing lymphocytes and dermal T6+ dendritic cells were found, while increased numbers of intratumoral T cells, inflammatory (27E10+) and mature (25F9+) macrophages were associated with local progression of primary melanomas. In metastases, most infiltrate components except 25F9+ macrophages were rare. Positive correlations were observed between: (1) dermal T6+ cells and IL-2 R+ lymphocytes, and (2) presence of IFN-gamma in the infiltrate and HLA-DR and gp89 antigens on tumor cells. In all stages, HLA-DR expression on tumor cells was correlated with: (1) a shift towards T8+ lymphocytes in the infiltrates and (2) a loss of IL-2 R expression. Our data suggest mutual influences between melanoma cells and mononuclear cell infiltrates in situ.

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

“…In none of the three aspirates positive staining of the tumour cells for MHC II was obtained, while in two of the three corresponding post-treatment tumour biopsies MHC II-positive tumour cells were detected (25 -50 and 75 -100%, respectively). As also found by others (Bröcker et al, 1984(Bröcker et al, , 1988Guerry et al, 1987;Hersey and Jamal, 1990), we found a close correlation between MHC II expression and presence of TIL. There was also a positive correlation between MHC II expression by tumour cells and regression of the lesion.…”

Association of microvessel density with infiltrating cells in human cutaneous malignant melanoma

“…Similarly, more intense macrophage infiltration in thicker melanomas has been reported by other observers. 7,62 Our results support the role of macrophages in vascularization of high-risk melanomas. According to Leek et al, monocytes are continually recruited into tumors, differentiate into tumorassociated macrophages, accumulate in hypoxic areas, and may induce angiogenesis through secretion of angiogenic cytokines including TNF-α, IL-1α and VEGF.…”

The chemokine RANTES is secreted by human melanoma cells and is associated with enhanced tumour formation in nude mice

“…Immunostimulating therapeutic approaches are primarily based on the migration to or the presence of leucocytes within the tumour tissue. Tumour-associated macrophages (TAM) can regularly be found in primary melanoma and melanoma metastasis and are, quantitatively, the dominating leucocyte type (Bršcker et al, 1988;Van Ravenswaay-Claasen et al, 1992). Analogous to inflammatory processes, the recruitment of monocytes from the peripheral blood into tumours such as melanomas is thought to be mediated mainly by chemotaxins.…”