Current research on immunopathology of melanoma: analysis of lymphocyte populations in relation to antigen expression and histological features of melanoma

Hersey, Peter; Murray, Elaine; Grace, Julienne; McCarthy, William H.

doi:10.3109/00313028509105490

Cited by 42 publications

(14 citation statements)

References 22 publications

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Most malignant tumors are accompanied by inflammatory infiltrates which, in all human solid tumors so far investigated, are mainly composed of T lymphocytes and macrophages (Allen and Hogg, 1985;Bhan and DesMarais, 1983;Gattringer et al, 1984; Gottlinger et al, 1985;Hersey et al, 1985;Hurlimann and Saraga, 1985;Kabawat et al, 1983;Kornstein et al, 1983;Poppema et al, 1983;Ralfkiaer et al, 1987;Rowe and Beverley, 1984;Ruiter et al, 1982). The cutaneous melanoma is an excellent model for tumor progression, since tumors at all stages, from intra-epidermally growing precursor lesions to highly invasive and metastatic tumors, are available for investigation.

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confidence: 99%

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

Bröcker

Zwadlo

Holzmann³

et al. 1988

Intl Journal of Cancer

140

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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.

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confidence: 99%

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

Bröcker

Zwadlo

Holzmann³

et al. 1988

Intl Journal of Cancer

140

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“…IgG concentrations in the supernatants of C281 and 14.18 were approximately 5-10 p~g/ml. C281 supernatant had a titer on melanoma tissue sections using avidin/biotin/immunoperoxidase techniques [18,21] of 1 : 4 (approximately 2.5 ~tg/ ml). C281 ascites had titers of approximately 1:200 (end titers taken as final dilution giving reactivity on sections).…”

Section: Materials Andmethodsmentioning

confidence: 99%

Potentiation of interleukin-2 production and its binding by monoclonal antibodies to the gangliosides GD3 and GD2

Schibeci

Hersey

Cheresh

1989

Cancer Immunol Immunother

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Previous studies have shown that monoclonal antibodies (mAbs) against certain gangliosides, which induced remissions in patients with melanoma, also potentiated the response of lymphocytes to a variety of stimuli, including lectins, interleukin-2 (IL-2) and antigens. The present studies have investigated the mechanism of these effects on lymphocytes. Although the mAbs potentiated phytohemagglutinin(PHA)-induced IL-2 production at high concentrations of mAbs and of PHA, this did not appear to explain their potentiation of the proliferative responses of lymphocytes. Hence, although IL-2 production was minimal or absent from the CD8+ subset the latter showed the highest degree of augmentation. Furthermore, addition of IL-2 to PHA-stimulated cultures did not produce similar augmentation of mitogenic responses to that produced by the mAb to GD3 or GD2. The augmented and normal mitogenic responses were, however, dependent on IL-2, as shown by their inhibition with mAbs against IL-2. The antiganglioside mAbs did not have significant effects on IL-2 receptor expression measured by mAbs to Tac. However, the mAbs appeared to increase the affinity of binding of radiolabelled IL-2 to IL-2 receptor and increased internalization of the latter. These results suggest that the effects of the mAbs on IL-2 production may be distinguished from their effects on the proliferative responses of T cells and that the latter were associated with changes in affinity and internalization of 125I-IL-2. Whether the latter is a direct cause of the increased proliferative response remains unknown. The ability of mAbs to GD2 and GD3 to increase IL-2 production and to "enhance" IL-2-dependent proliferative responses suggests the may have valuable clinical roles as immunopotentiating agents.

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“…10 The present study was designed to determine whether immunotherapy with a melanoma vaccine prepared from vaccinia melanoma cell lysates (VMCL) may reduce the risk of recurrence and improve OS in these groups of melanoma patients. The basis for this approach was, first, evidence that melanoma frequently induces an immune response as evidenced by signs of regression of primary melanoma 11 associated with lymphocytic infiltration into the tumor 12,13 and many in vitro studies showing antibody and T-cell responses to melanoma. 14,15 Second, prior studies in animal models had shown that viral infection of tumors could induce long-lasting immunity to the tumor.…”

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confidence: 99%

Adjuvant Immunotherapy of Patients With High-Risk Melanoma Using Vaccinia Viral Lysates of Melanoma: Results of a Randomized Trial

Hersey

Coates

McCarthy

et al. 2002

JCO

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140

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Current research on immunopathology of melanoma: analysis of lymphocyte populations in relation to antigen expression and histological features of melanoma

Cited by 42 publications

References 22 publications

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

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

Potentiation of interleukin-2 production and its binding by monoclonal antibodies to the gangliosides GD3 and GD2

Adjuvant Immunotherapy of Patients With High-Risk Melanoma Using Vaccinia Viral Lysates of Melanoma: Results of a Randomized Trial

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