The microenvironment in primary cutaneous melanoma with associated spontaneous tumor regression: evaluation for T-regulatory cells and the presence of an immunosuppressive microenvironment Journal Article


Authors: Gray, A; Grushchak, S; Mudaliar, K; Kliethermes, S.; Carey, K.; Hutchens, K. A.
Article Title: The microenvironment in primary cutaneous melanoma with associated spontaneous tumor regression: evaluation for T-regulatory cells and the presence of an immunosuppressive microenvironment
Abstract: Spontaneous tumor regression, regression in the absence of therapeutic intervention, can be identified histologically in over 25% of primary cutaneous melanomas at initial diagnosis. A unique subset of T lymphocytes found in areas of regression can be histologically distinguished from tumor-infiltrating T lymphocytes (TIL) found in areas of tumor progression. We call this unique subset of T lymphocytes regression-associated T lymphocytes (RATs). The aim of this study is to determine the phenotype of lymphocytes and the density of specific cell types linked to immunosuppression in areas of tumor progression compared with areas of tumor regression. These specific cell types include T-regulatory cells (Tregs) and S100A9 cells. A total of 14 primary cutaneous melanomas with areas of progression and regression were used. Immunohistochemistry staining was used to identify CD4 cells, CD8 cells, Tregs, and S100A9 cells. Two independent observers manually counted three high-powered x40 fields. There was no predominance of CD4 or CD8 T lymphocytes in either RATs or TIL. We identified a lower density of Tregs in RATs compared with TIL when using the FOXP3/CD4 Treg marker (P=0.04) and a marginal difference when using our second, confirmatory Treg marker, FOXP3/CD25 (P=0.11). We observed a lower density of S100A9 cells in RATs compared with TIL (P=0.002). There was an observable difference in the tumor microenvironments of RATs and TIL, with RATs having a significantly lower density of Tregs and S100A9 cells. We deduce that the absence of immunosuppression in areas of regression allows for a more robust immune response and thus effective eradication of tumor cells.
Keywords: Pathology
Journal Title: Melanoma research
Volume: 27
Issue: 2
ISSN: 1473-5636; 0960-8931
Publisher: Unknown  
Journal Place: England
Date Published: 2017
Start Page: 104
End Page: 109
Language: eng
DOI/URL:
Notes: LR: 20170302; JID: 9109623; ppublish