PD-1 mRNA expression in peripheral blood cells and its modulation characteristics in cancer patients

// Wei Wang 1 , Ge Shen 1 , Shikai Wu 1 , Shiping Song 1 , Yanli Ni 1 , Zhuoyao Suo 1 , Xiangying Meng 1 , Dan Li 1 , Lin Zhou 1 , Rimin Hao 1 , Yaowei Zhao 1 , Li Bai 1 , Lili Hou 1 , Bing Liu 1 and Guangxian Liu 1 1 Cancer Therapy Center, Affiliated Hospital of The Academy of Military Medical Sciences, Beijing 100071, China Correspondence to: Guangxian Liu, email: liugx270@hotmail.com Bing Liu, email: bingliu17@yahoo.com Keywords: PD-1, peripheral immune cells, immunomodulation, radiation therapy, cancer Received: June 15, 2016      Accepted: January 16, 2017      Published: February 02, 2017 ABSTRACT Immune checkpoint inhibitors that block the PD-1/PD-L1 signaling pathway have been used to treat a wide variety of cancers. Although results have been promising, significant inter-individual and inter-tumor variability has been observed. It is believed that better clinical outcome could be achieved if the treatment was individually designed based on the functional status of the PD-1/PD-L1 signaling and the cellular immunity. In this study, we analyzed the mRNA expression of PD-1 and other immunomodulatory genes in peripheral blood from cancer patients, and immunomodulatory gene expression during radiotherapy and immunomodulation therapy with cytokines. Our results show that the PD-1 mRNA expression is significantly increased in peripheral blood in cancer patients. Anti-cancer treatments can significantly modulate the PD-1 expression, but this is largely dependent on the initial immune status. Moreover, the PD-1 expression on peripheral lymphocytes can be immunoactivation-derived. These results suggest that the regulation and expression pattern of PD-1/PD-L1 signal is complicated which will influence the effect of blockade of the PD-1/PD-L1 signaling pathway for cancer treatment. Through combined analysis of PD-1, CTLA-4, and other immune markers in peripheral blood, we may accurately evaluate the functional status of PD-1/PD-L1 signaling and cellular immunity, thereby providing clues for guiding anti-PD-1 or anti-PD-L1 treatment.