Circulating PD‐1 (+) cells may participate in immune evasion in peripheral T‐cell lymphoma and chidamide enhance antitumor activity of PD‐1 (+) cells

• Published in: Cancer medicine (Malden, MA) Vol. 8; no. 5; pp. 2104 - 2113
• Main Authors: Zhang, Wei, Shen, Haorui, Zhang, Yan, Wang, Wei, Hu, Shaoxuan, Zou, Dongmei, Zhou, Daobin
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.05.2019; John Wiley and Sons Inc; Wiley
• Subjects: adaptive immune; Adaptive Immunity; Adult; Aged; Aminopyridines - administration & dosage; Aminopyridines - pharmacology; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Antitumor activity; Benzamides - administration & dosage; Benzamides - pharmacology; Case-Control Studies; Cell death; Chemotherapy; chidamide; Clinical Cancer Research; CTLA-4 Antigen - genetics; Cytomegalovirus; Cytotoxicity; Female; Flow cytometry; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Humans; Immune evasion; Immune response; Immunotherapy; innate immune; Innate immunity; Interferon; Interferon-gamma - metabolism; K562 Cells; Ligands; Lymphocytes; Lymphoma; Lymphoma, T-Cell, Peripheral - drug therapy; Lymphoma, T-Cell, Peripheral - genetics; Lymphoma, T-Cell, Peripheral - immunology; Male; Middle Aged; Original Research; Patients; peripheral T‐cell lymphoma; Programmed Cell Death 1 Receptor - blood; programmed cell death‐1; T-cell lymphoma; Tumor Escape; Young Adult; China; adaptive immune; chidamide; innate immune; peripheral T-cell lymphoma; programmed cell death-1
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.2097

Peripheral T‐cell lymphoma (PTCL) is a heterogeneous disease with poor outcomes. We intend to explore the role of circulating PD‐1 (+) cells in tumor immune evasion in PTCL patients and the mechanism of chidamide as a regulator of immune‐associated medicine on PD‐1 (+) cells. Gene expression profiling (GEP) was performed on circulating PD‐1 (+) cells from 22 PTCL patients and 13 healthy subjects, and circulating PD‐1 (−) cells from 2 PTCL patients. PD‐1 (+) cells were treated with chidamide, and the production IFN‐γ and cytotoxicity were analyzed. GEP were performed on circulating PD‐1 (+) cells from 2 PTCL patients treated with chidamide combined with chemotherapy and 1 patient treated with traditional chemotherapy. GEP showed that genes associated with innate immune response were abnormally expressed in PD‐1 (+) cells of PTCL patients compared with healthy subjects, meanwhile the expression of CTLA‐4 was significantly higher in PD‐1 (+) cells than that of PD‐1 (−) cells. In vitro study revealed decreased level of IFN‐γ secretion and impaired cytotoxic activity of PD‐1 (+) cells compared with PD‐1 (−) cells, while chidamide could recover the deficiencies and upregulate adaptive immune‐associated genes in PD‐1 (+) cells of PTCL patients. Our research indicated that PD‐1 (+) cells might have deficiencies in innate and adaptive immune response and chidamide may reverse the defects. These figures showed that the gene expression of PD‐1 (+) cells in peripheral blood of PTCL patients was different from that of healthy controls (Figures 1 and 2), and anti‐tumor effects of PD‐1 (+) cells were weaker than that of PD‐1 (‐) cells (Figures 3 and 4), while chidamide could normalize tumor immunity by regulating immune‐associated genes of PD‐1 (+) cells (Fig. 5).