Differential Upregulation of Th1/Th17-Associated Proteins and PD-L1 in Granulomatous Mycosis Fungoides

Authors

Mario L Marques-Piubelli
Jesus Navarrete
Debora A Ledesma
Courtney W Hudgens
Rossana N Lazcano
Ali Alani
Auris Huen
Madeleine Duvic
Priyadharsini Nagarajan
Phyu P Aung
Ignacio I Wistuba
Jonathan L Curry
Roberto N Miranda
Carlos A Torres-Cabala

Publication Date

2-27-2024

Journal

Cells

Abstract

Granulomatous Mycosis Fungoides (GMF) is a rare form of mycosis fungoides (MF) characterized by a granulomatous infiltrate associated with the neoplastic lymphoid population and is considered to have a worse prognosis compared with regular MF. The upregulation of the T helper (Th) axis, especially Th17, plays an important role in the pathogenesis of several inflammatory/infectious granulomatous cutaneous diseases, but its role in GMF is still not elucidated to date. In this study, we evaluated the immunohistochemical expression of Th1 (Tbet), Th2 (GATA-3), Th17 (RORγT), T regulatory (Foxp3), and immune checkpoint (IC) (PD-1 and PD-L1) markers in a cohort of patients with GMF and MF with large cell transformation (MFLCT). Skin biopsies from 49 patients (28 GMF and 21 MFLCT) were studied. Patients with GMF were associated with early clinical stage (p = 0.036) and lower levels of lactate dehydrogenase (p = 0.042). An increased percentage of cells positive for Tbet (p = 0.017), RORγT (p = 0.001), and PD-L1 (p = 0.011) was also observed among the GMF specimens, while a stronger PD-1 intensity was detected in cases of MFLCT. In this cohort, LCT, RORγT < 10%, Foxp3 < 10%, age, and advanced stage were associated with worse overall survival (OS) in univariate analysis. GMF demonstrated Th1 (cellular response) and Th17 (autoimmunity) phenotype, seen in early MF and granulomatous processes, respectively, which may be related to the histopathological appearance and biological behavior of GMF. Further studies involving larger series of cases and more sensitive techniques are warranted.

Keywords

Humans, Nuclear Receptor Subfamily 1, Group F, Member 3, Skin Neoplasms, B7-H1 Antigen, Up-Regulation, Programmed Cell Death 1 Receptor, Glia Maturation Factor, Mycosis Fungoides, Forkhead Transcription Factors

Comments

Supplementary Materials

PMID: 38474383