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 ×40 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.

Chemical carcinogen safety testing: OECD expert group international consensus on the development of an integrated approach for the testing and assessment of chemical non-genotoxic carcinogens

“…If exposure stops within a certain timeframe, at specific time points before the tipping or threshold point prior to an atypical change in proliferation or tissue morphology, the process towards adversity may be halted and the extent of damage may decrease with no or reduced exposure, depending on the specific real-life situation, where other stressors come into play (e.g. (Gray et al 2017 ; Parsons et al 2010 ; Robsahm et al 2019 ; Sakamaki et al 2017 ).…”

Intratumoral T-Lymphocyte Subsets in Canine Oral Melanoma and Their Association With Clinical and Histopathological Parameters

“…Twenty-three were female and 22 were male, and all dogs were castrated or spayed. The most represented breeds were mixed breed (18), Teckel (5), and English Cocker Spaniel (4). Of the 50 samples received, 34 were the first occurrence of melanoma and 16 were local recurrences.…”

A long-term survivor with esophageal melanoma and pulmonary metastasis after single-stage esophagectomy and lobectomy

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