Upregulation of Inhibitory Signaling Receptor Programmed Cell Death-1 (PD1) in Disease Evolution from Epitheliotropic T-Cell Dyscrasia (ETCD) to Mycosis Fungoides (MF).
Xuan Wang, Cynthia M Magro. New York Presbyterian Hospital-Weill Cornell Medical Center, NY
Background: Negative immunoregulatory checkpoints impede effective immune responses to tumor and reduce the action of anticancer agents. One such example is PD1, an inhibitory signaling receptor expressed on activated and CD4+CD25+foxp3+ suppressor T cells. PD1 ligand binding leads to inhibition of cytokine secretion by CD4+ T cells. Upregulation of PD1 has been suggested to be associated with disease progression in various tumors; however, whether PD1 plays a role in pathogenesis of MF is not clear.
Design: Skin biopsies were studied from 19 patients with MF, 6 with ETCD/large plaque parapsoriasis (LPP), and 1 with overlap features between LPP and early MF. IHC studies for PD1 and selected T-cell markers were performed, as well as T-cell clonality analysis.
Results: In 5/6 cases of ETCD/LPP, very few atypical lymphocytes exhibited PD1-positivity. In sharp contrast, focal strong staining of PD1 was observed in the neoplastic cells of 18/19 cases of MF.
The percentage of PD1-positive lymphocytes was also consistently higher in tumor stage than in patch and plaque stage MF. Interestingly, in the case where there was overlap between LPP and early MF, the number of PD1-positive lymphocytes approximated that seen in patch and plaque stage MF. Moreover, one patient presented skin biopsies at different stages of disease evolving from LPP to PMF, with a concomitant increase of PD1 expression between the biopsies.
Conclusions: Upregulation of PD1 correlates with disease progression in ETCD ranging from minimal staining in prelymphomatous dyscrasias to significant staining amidst neoplastic cells in more aggressive disease, likely reflecting the effects of PD1 on inhibiting tumor surveillance regulatory T cell populations. This observation thus raises the possibility to target PD1 for immunomodulation in MF therapy.
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 106, Wednesday Afternoon