Tumour-infiltrating lymphocytes in metastatic malignant melanoma and response to interferon alpha treatment

Abstract

Summary Interferon alpha (IFN-a) has a documented activity against malignant melanoma with a response rate of only approximately 20%. It would therefore be of considerable importance if patients likely to respond could be identified. The degree of mononuclear cell infiltration in primary tumours has been reported to correlate with a favourable prognosis. This investigation used monoclonal antibodies, anti-CD4, -CD8 and -CD 1 lc, to identify subsets of tumour-infiltrating mononuclear cells in fine needle aspirates to study whether the presence of such cells correlates with the therapeutic effect of IFN-a. Twenty-one patients with systemic and 20 with regional metastatic malignant melanoma were studied before initiation of IFN-a treatment. A statistically significant correlation (P<0.001) was found between the occurrence of CD4+ lymphocytes in fine needle aspirates and the therapeutic benefit of IFN-a in patients with systemic disease. Ten out of 11 with moderate to high numbers of infiltrating CD4+ lymphocytes achieved tumour regression. In contrast, among patients with low numbers of these cells in metastatic lesions, nine out of ten had progressive disease. Similar results were found in patients with regional disease.

Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival

“…Our results demonstrate that immune effector cells localise to sites of tumour in responding patients and that both CD4 and CD8 T-cell subsets are requisite for the response to IL-2 based immunotherapy. This is in accordance with findings in metastatic malignant melanoma treated with IL-2 (Rubin et al, 1989) and IFN-a (Hakansson et al, 1996;2001). Thus, there seems to be a causative relationship between intratumoral lymphocyte subsets and both response and survival, as indicated by the fact that progressing patients had very few intratumoral lymphocyte subsets at both baseline and during treatment.…”

Immunoreactivity with the Anti-MAGE Antibody 57B in Malignant Melanoma: Frequency of Expression and Correlation with Prognostic Parameters

“…Two recent studies have also examined tumorinfiltrating lymphocytes in metastatic tumors and revealed evidence that patients had a longer disease-free survival, if their metastatic tumor deposits were involved by a brisk lymphocytic infiltrate (41,42). In contrast with primary tumors, we did not find a correlation between 57B immunopositivity and the density of the lymphocytic infiltrate of metastatic tumor deposits.…”

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

“…The occurrence of tumour regression was evaluated by histopathological examination of tumour biopsies based on the description of regressive changes in malignant melanoma as previously described (McGovern, 1975;Kang et al, 1993;Håkansson et al, 1996Håkansson et al, , 1998. The following criteria of tumour regression were used in this study: (1) low and variable density of tumour cells, particularly variation in density within the same tumour nodule; (2) disorganisation of the architecture of the tumour with nests of remaining tumour cells surrounded by stromal tissue and (3) fibrosis.…”