Gene Expression Shows New Mechanism of Action With Chidamide Therapy in Peripheral T-Cell Lymphoma


alopah Date:2021-07-21 11:02:18 From:hematologyadvisor
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In a new study, researchers identified a possible immune-related mechanism of action associated with chidamide in treatment of patients with peripheral T-cell lymphomas (PTCLs) who were given a combination of chidamide and chemotherapy. The study’s results were published in Frontiers in Oncology.

 

Chidamide is a member of the drug class known as histone deacetylase inhibitors, which have antitumor effects in terms of induction of apoptosis and arrest of the cell cycle. However, these agents also may possess immune-related antitumor activity, the researchers explained in their report. The research team set out to examine whether chidamide can influence circulating levels of programmed cell death protein 1 (PD-1)-positive cells, in conjunction with treatment response.
Patients with a newly diagnosed PTCL were included in this study. All patients received both chidamide and chemotherapy, with chemotherapy consisting of cyclophosphamide, epirubicin, vindesine, prednisone, and etoposide (CHOEP). Gene expression profile analysis was conducted using the messenger RNA of PD-1(+) peripheral blood mononuclear cells before and following the end of first-line treatment.

 

chidamide

 

Differentially expressed genes (DEGs) were identified using an EBseq algorithm and based on patient responses of achieving complete remission (CR) or not achieving CR, according to 2014 Lugano classification criteria. DEGs were evaluated primarily based on pretreatment and posttreatment expression levels, and they were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) tools.

 

A total of 9 patients were evaluated, 5 of whom achieved CR. In the CR group, a total of 302 DEGs were found, with 162 of the genes upregulated and 140 of the genes downregulated. The non-CR group was found to have 12 DEGs.

 

From patients in the CR group, the 15 most significant upregulated DEGs identified through GO analysis were related to chemokine activity, chemotaxis, and responses to interleukin-1 and interferon-g. A gene concept network of these 15 most significant DEGs in GO analysis indicated these genes were members of the C-C chemokine family. The 15 most significant upregulated DEGs identified through KEGG analysis revealed associations with pathways involving cytokine-cytokine receptor interactions and chemokine signaling.

 

“In conclusion, we report here for the first time that chidamide treatment enhanced the expression of genes associated with chemokine activity and chemotaxis function of circulating PD-1(+) cells from patients with PTCLs,” the researchers wrote in their report. They also concluded that these findings may support a rationale of combining chidamide with PD-1 inhibitors in treatment of PTCLs.

 

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