Upregulation of inhibitory signaling receptor programmed death marker-1 (PD-1) in disease evolution from cutaneous lymphoid dyscrasias to mycosis fungoides and Sezary's syndrome.
Academic Article
Overview
abstract
BACKGROUND: Negative immunoregulatory checkpoints impede effective immune responses to tumor and reduce the action of anticancer agents. One such example is programmed death marker-1 (PD-1), an inhibitory signaling receptor expressed on activated and regulatory T-cells. PD-1 expression was reported in a few reports, but the expression profile of PD-1 and mycosis fungoides (MF) remains largely to be characterized. DESIGN: In this study, skin biopsies from 42 prelymphomatous T-cell dyscrasias (CLD), 9 Sezary's syndrome (SS), 103 MF, and 20 CD30+ lymphoproliferative diseases (LPD) were examined for PD-1 expression using immunohistochemistry. RESULTS: PD-1 staining was observed amidst many neoplastic T-cells in 6/9(66.7%) and 62/103 (60.2%) cases of SS and MF respectively, while only 6/42 (14.3%) cases of CLD and 0/20 (0%) cases of CD30+ LPD (P<0.001). Three cases are from same patients representing different stages of disease evolution from CLD to MF and SS with a corresponding enrichment of PD-1 positivity. In all cases there was variable staining of PD-1 amidst macrophages. There was no correlation with disease progression among MF cases. Twenty cases of CD30+ LPD did not show any PD-1 positivity. CONCLUSION: PD-1 seems to correlate with disease progression in epitheliotropic T cell dyscrasias ranging from minimal staining in prelymphomatous dyscrasias to significant staining in MF, likely reflecting the effects of PD-1 on inhibiting tumor surveillance regulatory T cell populations. PD-1 was consistently expressed in MF while it was consistently negative in primary CD30+ LPD, suggesting the possibility of using PD-1 as a means of distinguishing CD30+ MF from primary cutaneous ALCL.
