Cellular interaction of mycosis fungoides tumor cells changes from cytotoxic CD8+ T cells in plaques to B cells in tumors.

INTRODUCTION

Mycosis Fungoides (MF) is characterized by the proliferation of malignant skin-homing memory CD4+ T cells. The disease typically follows an indolent course, progressing from plaques (scaly, erythematous skin lesions) in the early stages (Ia-Ib) to tumors (>IIb) in approximately one-third of cases. Although recent studies have explored cell phenotypes and counts of the tumor microenvironment (TME) in MF progression, spatial interactions between tumor and reactive cells remain poorly understood.

METHODS

We performed a comprehensive high-dimensional analysis of immune cell composition and cellular interactions across MF stages using a custom Imaging Mass Cytometry (IMC) panel to examine the spatial complexity of the MF TME.

RESULTS

Stage-specific changes in the TME included an increased percentage of cytotoxic CD8+ cells in plaques and an increased percentage of B cells and dendritic cells in tumors. With progression of disease shift in the spatial organization of the TME was observed, from CD8+ T cell-tumor cell and monocyte-CD4+ T cell interactions in plaques to B cell-tumor cell interactions in tumors.

DISCUSSION: A stage-dependent shift in interactions from anti-tumor immune responses to features consistent with immune evasion mechanisms has been observed with the progression of MF. These insights underscore the importance of spatial context in understanding MF progression and highlight therapeutic targets that could inform stage-specific (immune)therapies.