Tumor metastasis biopsy as a surrogate marker of response to melanoma immunotherapy

In patients undergoing immunotherapy for metastatic melanoma, the clinical response in immunotherapeutic trials may be partial or difficult to detect. Tumor metastasis biopsy allows direct characterisation of an anti-tumor im munological response. During a phase I/II trial of granulocyte macrophage c olony stimulating factor (GM-CSF) transduced autologous melanoma immunother apy, the cellular response was examined by immunohistochemical analysis in a limited number of tumor biopsies taken from patients who either responded or progressed. Clinical response was associated with tumor infiltration by CD4+ and CD8+ T-cells, macrophages and differentiated dendritic cells (DC) , and expression of HLA-DR by the tumor cells. This tumor infiltration was associated with increased melanoma-specific peripheral blood precursor cyto toxic T-lymphocyte (pCTL) and the ability to obtain tumor-infiltrating lymp hocytes in vitro. In contrast, progression or a lack of clinical response w as associated with a lack of T-cell and DC infiltration into the tumor tiss ue in all such biopsies. Macrophages and eosinophils infiltrated these tumo rs, while T-cells and DC were present at some distance from the tumor. Thes e preliminary data strongly suggest that the location and extent of T-cell and DC infiltration, as well as the expression of HLA-DR by tumor cells are associated with a clinical response in this form of melanoma immunotherapy .