The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies

Abstract

T-cell activation and dysfunction relies on direct and modulated receptors. Based on their functional outcome, co-signaling molecules can be divided as co-stimulators and co-inhibitors, which positively and negatively control the priming, growth, differentiation and functional maturation of a T-cell response. We are beginning to understand the power of co-inhibitors in the context of lymphocyte homeostasis and the pathogenesis of leukemia, which involves several newly described co-inhibitory pathways, including the programmed death-1 (PD-1) and PD-1 ligand (PD-L1) pathway. The aim of this review is to summarize the PD-1 and PD-L1 biological functions and their alterative expression in hematological malignancies. The role of PD-1 and PD-L1 in T-cell immune suppression and the potential for immunotherapy via blocking PD-1 and PD-L1 in hematological malignancies are also reviewed.

Expression of PD-L1 Identifies a Subgroup of More Aggressive Non-Small Cell Carcinomas of the Lung

“…PD-1 is expressed on activated T cells and interacts with its ligands PD-L1 (B7-H1) and PD-L2 (B7-DC), leading to the reduced proliferation, exhaustion and apoptosis of T cells [8,9]. PD-1 is also expressed on a subset of thymic T cells, NK cells, B cells, monocytes and dendritic cells [8,10,11,12]. The main ligand of PD-1 is PD-L1, which is an important member of the B7/CD28 costimulatory factor superfamily and is expressed on T cells, dendritic cells and macrophages in order to regulate an adequate immune response [13,14].…”

Clinical, molecular, and immunological responses to pembrolizumab treatment of synchronous melanoma and acute myeloid leukemia

“…12 So far, only limited clinical data are available on the pattern of PD-L1 or PD-1 expression on T cells in patients with myeloid disease. 13 We found that PD-L1 and PD-1 expression also increased on PB-and BM-derived T cells during PEM therapy (Figure 2C-F; supplemental Figure 1). The direct relationship of these findings to PEM therapy is supported by the observation that T cells also showed a marked reduction of PD-L1 and PD-1 expression in PB during treatment interruption.…”

Arsenic induced complete remission in a refractory T-ALL patient with a distinct T-cell clonal evolution without molecular complete remission: A case report

“…Previous studies have shown that TCR repertoire deficiency is a common characteristic of patients with leukemia, including those with T-ALL (12,46). Potential reasons for deficiencies in the TCR repertoire include: i) The prior proliferation of a malignant T-cell clones suppressed the proliferation of normal T-cell clones, and ii) the tumor microenvironment or other unknown factors affect the competency of the immune system (47,48). However, the T-cell repertoire deficiency was not significantly reconstituted even when the patient achieved CR, as the reconstitution of the TCR repertoire is slow due to the cytotoxicity of chemotherapy (49).…”