Variability of PD-L1 expression in mastocytosis

Abstract

Key Points• PD-L1 is variably expressed in MCs from patients with SM and CM.• PD-1 is expressed in MCs in a subset of patients with CM, but not SM.

PD-L1 Expression in Mastocytosis

“…While PD-1 expression was present in a subset of CM cases reported by both Katoaka et al and Hatch et al, interestingly, PD-L1 expression was limited to neoplastic mast cells and was not reported in tumor infiltrating lymphocytes [13,16]. The presence of a T-cell lymphocytic infiltrate in association with the neoplastic mast cell infiltrates in the spleen may suggest a cytokine-mediated mechanism of the PD-L1 expression, which could be consistent with the variability of the PD-L1 expression identified within neoplastic mast cells, even within the same tissue in a given patient [16]. In cases with no identifiable or limited T-cell infiltrates, an underlying genetic or epigenetic mutation may underlie an increased PD-L1 expression by the neoplastic mast cells.…”

“…Interestingly, in the bone marrow of patients with SM, lymphoid infiltrates are seen more frequently in indolent SM, whereas the bone marrow from patients with advSM typically lacks significant lymphocytic infiltrates (personal observations, T.I.G). This may have implications for the efficacy of immune checkpoint therapies both between patients and within different tissues in a single patient [16].…”

“…In 2018, Hatch et al examined PD-1 and PD-L1 by IHC in 55 tissues from patients with mastocytosis, demonstrating a PD-L1 expression in 77% of bone marrow biopsies and 92% of skin biopsies including all mastocytosis types; they found no expression of PD-1 or PD-L1 within mast cells in healthy or reactive bone marrows or cases of myelodysplastic syndrome or myeloproliferative neoplasms [16]. PD-L1 surface expression was confirmed by flow cytometry in patients with ISM and ASM.…”

“…PD-L1 staining in neoplastic mast cells using multicolor immunohistofluorescence (see methods in Hatch et al, 2018 [16]): ( A ) spleen tissue from a patient with mast cell leukemia, stained for mast cells (tryptase, red) and programmed death-ligand 1(PD-L1) (light green); ( B ) skin from a patient with cutaneous mastocytosis, stained for mast cells (tryptase, red), PD-L1 (light green), and nuclei (4’,6-diamidino-2-phenylindole (DAPI), blue).…”

Mast Cells: Fascinating but Still Elusive after 140 Years from Their Discovery

“…Another group of mastocytosis experts demonstrate the expression of programmed death ligand 1 (PD-L1) on mast cells from patients with mastocytosis [58]. PD-L1 is expressed on tumor cells [59,60] and also on several activated immune cells, including CD4 + and CD8 + T cells, B cells, NKT cells, and mast cells [61][62][63]. PD-L1 expression has been shown to be upregulated in several tumor cells as a mechanism of immune suppression and evasion [64].…”