Expression of PD‐L1 on regulatory B cells in patients with acute myeloid leukaemia and its effect on prognosis

Shi, Yingqing; Liu, Zhuogang; Wang, Hongtao

doi:10.1111/jcmm.17390

Cited by 7 publications

(5 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the pembrolizumab therapy of myeloid malignancies relapsing after allo-HCT, subjects with a high expression of PD-L1 within lymphoma cells showed a substantial complete response to therapy [ 40 ]. That might be related to the predominance of CD19+ cells that, together with regulatory B cells (Breg), were shown as a great source of PD-L1 in AML [ 13 ]. In AML subjects aged above 65 years, there were no improvements in the chemotherapy (azacytidine) outcomes when blocking of PD-L1 with PD-1 was introduced using durvalumab.…”

Section: Discussionmentioning

confidence: 99%

“…These data supported the disadvantageous role of tumour-related PD-L1 in AML patients, in which high levels were associated with significantly worse survival [ 12 ]. Importantly, the poor prognosis was also reported in AML subjects with high PD-L1 within regulatory B cells, being possibly another target for specific therapy [ 13 ]. The protein of the B7 family, B7-H3, is another checkpoint with exclusively high expression in AML compared to other haematological malignancies and healthy controls [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Association between Immune Checkpoint Proteins and Therapy Outcomes in Acute Myeloid Leukaemia Patients

Bolkun,

Tynecka,

Walewska

et al. 2023

Cancers

View full text Add to dashboard Cite

The development of novel drugs with different mechanisms of action has dramatically changed the treatment landscape of AML patients in recent years. Considering a significant dysregulation of the immune system, inhibitors of immune checkpoint (ICI) proteins provide a substantial therapeutic option for those subjects. However, use of ICI in haematological malignancies remains very limited, in contrast to their wide use in solid tumours. Here, we analysed expression patterns of the most promising selected checkpoint-based therapeutic targets in AML patients. Peripheral blood of 72 untreated AML patients was used for flow cytometric analysis. Expression of PD-1, PD-L1, CTLA-4, and B7-H3 was assessed within CD4+ (Th) lymphocytes and CD33+ blast cells. Patients were stratified based on therapy outcome and cytogenetic molecular risk. AML non-responders (NR) showed a higher frequency of PD-1 in Th cells compared to those with complete remission (CR). Reduced blast cell level of CTLA-4 was another factor differentiating CR from NR subjects. Elevated levels of PD-1 were associated with a trend for poorer patients’ survival. Additionally, prognosis for AML patients was worse in case of a higher frequency of B7-H3 in Th lymphocytes. In summary, we showed the significance of selected ICI as outcome predictors in AML management. Further, multicentre studies are required for validation of those data.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Association between Immune Checkpoint Proteins and Therapy Outcomes in Acute Myeloid Leukaemia Patients

Bolkun,

Tynecka,

Walewska

et al. 2023

Cancers

View full text Add to dashboard Cite

show abstract

“…Regulatory B cells (Bregs), immunomodulatory B cells that exert immunomodulatory effects mainly via secreting various soluble mediators including IL-10 are reported to increase in peripheral blood as well as bone marrow samples in AML patients, highlighting their role in the AML pathogenesis (171). Recently, PD-L1 expression has been reported on Bregs in AML patients and is associated with a worse prognosis (165). According to an in-vivo study, CXCL13 has been suggested as a novel IC regulating Breg activity where ablation of CXCL13 increased the efficacy of chemotherapy and PD-1 blockade, though this study did not involve an AML model (172).…”

Section: B Cellsmentioning

confidence: 96%

“…Resident T cells from AML bone marrow samples of AML patients were reported to have altered transcription profiles expressing genes related stemness and myeloid priming (163). Increased frequency of PD-1+CD4+ and ICOS+/CD4+ effector T cells were reported in the BM samples of AML patients (164,165). In terms of Tregs, their proportion in the BMM was reported to be higher compared to healthy controls, and a higher frequency of PD-1 + /CD8 + cells co-expressing TIM3 or LAG3 was detected, especially in patients who had multiply relapsed AML.…”

Section: T Cellsmentioning

confidence: 99%

A potential area of use for immune checkpoint inhibitors: Targeting bone marrow microenvironment in acute myeloid leukemia

et al. 2023

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) arises from the cells of myeloid lineage and is the most frequent leukemia type in adulthood accounting for about 80% of all cases. The most common treatment strategy for the treatment of AML includes chemotherapy, in rare cases radiotherapy and stem cell and bone marrow transplantation are considered. Immune checkpoint proteins involve in the negative regulation of immune cells, leading to an escape from immune surveillance, in turn, causing failure of tumor cell elimination. Immune checkpoint inhibitors (ICIs) target the negative regulation of the immune cells and support the immune system in terms of anti-tumor immunity. Bone marrow microenvironment (BMM) bears various blood cell lineages and the interactions between these lineages and the noncellular components of BMM are considered important for AML development and progression. Administration of ICIs for the AML treatment may be a promising option by regulating BMM. In this review, we summarize the current treatment options in AML treatment and discuss the possible application of ICIs in AML treatment from the perspective of the regulation of BMM.

show abstract

“…PD-1 expression is generally high on T cells in AML patients with de novo and relapsed/refractory (R/R) after chemotherapy, and partial recovery is achieved in patients with complete remission ( 47 – 49 ). Moreover, the level of PD-1 on NK cells and PD-L1 on regulatory B cells (Bregs) increases in AML patients ( 47 , 48 , 50 , 51 ). High expression of PD-1 coincides with the T-cell exhaustion ( 52 – 54 ).…”

Section: Role Of Pd-1/pd-l1 In the Development Of Leukemiamentioning

confidence: 99%

Progress of research on PD-1/PD-L1 in leukemia

Cao,

Wu,

Zhou

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

Leukemia cells prevent immune system from clearing tumor cells by inducing the immunosuppression of the bone marrow (BM) microenvironment. In recent years, further understanding of the BM microenvironment and immune landscape of leukemia has resulted in the introduction of several immunotherapies, including checkpoint inhibitors, T-cell engager, antibody drug conjugates, and cellular therapies in clinical trials. Among them, the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis is a significant checkpoint for controlling immune responses, the PD-1 receptor on tumor-infiltrating T cells is bound by PD-L1 on leukemia cells. Consequently, the activation of tumor reactive T cells is inhibited and their apoptosis is promoted, preventing the rejection of the tumor by immune system and thus resulting in the occurrence of immune tolerance. The PD-1/PD-L1 axis serves as a significant mechanism by which tumor cells evade immune surveillance, and PD-1/PD-L1 checkpoint inhibitors have been approved for the treatment of lymphomas and varieties of solid tumors. However, the development of drugs targeting PD-1/PD-L1 in leukemia remains in the clinical-trial stage. In this review, we tally up the basic research and clinical trials on PD-1/PD-L1 inhibitors in leukemia, as well as discuss the relevant toxicity and impacts of PD-1/PD-L1 on other immunotherapies such as hematopoietic stem cell transplantation, bi-specific T-cell engager, chimeric antigen receptor T-cell immunotherapy.

show abstract

Expression of PD‐L1 on regulatory B cells in patients with acute myeloid leukaemia and its effect on prognosis

Cited by 7 publications

References 31 publications

The Association between Immune Checkpoint Proteins and Therapy Outcomes in Acute Myeloid Leukaemia Patients

The Association between Immune Checkpoint Proteins and Therapy Outcomes in Acute Myeloid Leukaemia Patients

A potential area of use for immune checkpoint inhibitors: Targeting bone marrow microenvironment in acute myeloid leukemia

Progress of research on PD-1/PD-L1 in leukemia

Contact Info

Product

Resources

About