Background: Immune checkpoints are involved in mechanisms by which tumours escape from the host immune system. Our aim was to evaluate acute myeloid leukaemia (AML) patients to determine expression levels of checkpoint molecules according to diagnosis and treatments, and to identify optimal candidates for checkpoint blockade.
Methods: Bone marrow (BM) samples were obtained from 279 AML patients at different disease status and from 23 controls. Flow cytometric analyses of PD-1 and PD-L1/PD-L2 expression were performed.
Results: Programmed death-1 (PD-1) expression levels on CD8 T-cells at AML diagnosis were increased compared to controls. PD-L1 and PD-L2 expression levels on leukaemic cells at diagnosis were significantly higher in secondary AML than in AML. PD-1 levels on CD8 and CD4 T-cells after allo-SCT were significantly higher than those at diagnosis and after CTx. PD-1 expression on CD8 T-cells increased in the acute GVHD group than in the non-GVHD group. The overall survival of patients with high PD-1 expression on CD8 T-cells was significantly shorter than that of patients with low PD-1 expression.
Conclusions: In conclusion, patients who underwent allo-SCT exhibited high PD-1 expression, suggesting that allo-SCT increases PD-1 expression on T-cells, and the patients with high PD-1 expression on CD8 T-cells after allo-SCT showed the poor prognosis. For these patients, PD-1 blockade could be an immunotherapeutic strategy.
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http://dx.doi.org/10.1177/00045632231184716 | DOI Listing |
In Vivo
December 2024
Immunotherapy Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan;
Background/aim: Immune checkpoint blockade has achieved great success as a targeted immunotherapy for solid cancers. However, small molecules that inhibit programmed death 1/programmed death ligand 1 (PD-1/PD-L1) binding are still being developed and have several advantages, such as high bioavailability. Previously, we reported a novel PD-1/PD-L1-inhibiting small compound, SCL-1, which showed potent antitumor effects on PD-L1 tumors.
View Article and Find Full Text PDFCancer Lett
December 2024
Department of Medicine, Section of Epidemiology and Population Sciences, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:
The p53 tumor suppressor is commonly mutated in cancer; however, there are no effective treatments targeting p53 mutants. A DNA vaccine gWIZ-S237G targeting the p53 S237G mutant, which is highly expressed in A20 murine tumor cells, was developed and administered intramuscularly via electroporation, either alone or in combination with PD1 blockade. The anti-p53-S237G immunization elicited a robust protective response against subcutaneous A20 tumors and facilitated the infiltration of immune cells including CD8 T cells, NK cells, and DCs.
View Article and Find Full Text PDFHum Immunol
December 2024
Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:
The immune checkpoint receptors play a crucial role in managing the transplantation outcome including development of acute graft versus host disease (aGVHD) and disease recurrence following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is well established. This study aimed to investigate the expression of immune checkpoint receptors, including PD-1/PD-L1, CTLA-4, TIM-3, and LAG-3 in donors, as well as changes in their expression during the first 90 days (day 30 and day 90) post-HLA-matched allo-HSCT, concerning the development of aGVHD and disease relapse. Forty-one donor/recipient pairs were included in this study.
View Article and Find Full Text PDFJ Cell Mol Med
December 2024
Department of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Gliomas are the most prevalent form of primary brain tumours. Recently, targeting the PD-1 pathway with immunotherapies has shown promise as a novel glioma treatment. However, not all patients experience long-lasting benefits, underscoring the necessity to discover reliable biomarkers for predicting treatment outcomes.
View Article and Find Full Text PDFBr J Dermatol
December 2024
Department of Dermatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Background: The tumour microenvironment significantly influences the clinical response of patients to therapeutic immune checkpoint inhibition (ICI), but a comprehensive understanding of the underlying immune-regulatory proteome is still lacking.
Objectives: To decipher targetable biologic processes that determine tumour-infiltrating lymphocytes (TiLs) as a cellular equivalent of clinical response to ICI.
Methods: We mapped the spatial distribution of proteins in TiL-enriched vs.
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