Circulating PD‐1 (+) cells may participate in immune evasion in peripheral T‐cell lymphoma and chidamide enhance antitumor activity of PD‐1 (+) cells. (10th April 2019)

• Record Type: Journal Article
• Authors: Zhang, Wei; Shen, Haorui; Zhang, Yan; Wang, Wei; Hu, Shaoxuan; Zou, Dongmei; Zhou, Daobin
• Is Part Of: Cancer medicine. Volume 8:Number 5(2019:May)
• Page Start: 2104
• Page End: 2113
• Publication Date: 2019-04-10
• Subjects: adaptive immune -- chidamide -- innate immune -- peripheral T‐cell lymphoma -- programmed cell death‐1; 616.994005
• DOI: 10.1002/cam4.2097
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: 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. Abstract : 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).