Profile of PD-1 and PD-L1 mRNA Expression in Peripheral Blood of Nasopharyngeal Carcinoma
Abstract
Background: Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) expression is associated with prognostic and respond to immunotherapy with immune checkpoint inhibitor in several solid malignancies. However, the prognostic roles of PD-1 and PD-L1 expression in nasopharyngeal carcinoma (NPC) are less clear. This study aims to investigate PD-1 and PD-L1 mRNA expression levels in peripheral blood of Indonesian NPC patients and its association with clinicopathological features.
Materials and Methods: This study used blood samples of 21 NPC patients and 10 healthy volunteers as controls. Real-time polymerase chain reaction (PCR) was used to measure mRNA expression of PD-1 and PD-L1.
Results: PD-1 mRNA expression levels were significantly lower in NPC patients (∆CT mean: 9.65±2.04) compared to healthy individuals (∆CT mean: 8.04±1.51) (p=0.031). In contrast, PD-L1 mRNA expression levels were higher in NPC patients (∆CT mean: 6.96±1.32) compared to healthy individuals (∆CT mean: 7.11±0.55), but the difference was not statistically significant (p=0.554). The expression of PD-1 was associated with tumour-node-metastasis (TNM) stage (p=0.030) but not associated with age (p=1.000), sex (p=1.000), body mass index (p=0.350), tumor stage (p=0.338), nodal stage (p=0.579), metastasis stage (p=0.371), and Eastern Cooperative Oncology Group (ECOG) status (p=0.228). Meanwhile PD-L1 expression was not associated with all clinicophatological features.
Conclusion: The PD-1 mRNA expression levels were significantly lower, while PD-L1 expression levels were higher in NPC patients compared to healthy controls. PD-1 expression was correlated with TNM stage.
Keywords: nasopharyngeal carcinoma, immune checkpoint inhibitors, PD-1, PD-L1
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World Health Organization. NASOPHARYNGEAL CARCINOMA: Union for International Cancer Control, 2014 Review of Cancer Medicines on the WHO List of Essential Medicines. Geneva; WHO: 2014, article.
Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, MacIntyre MF, et al. The global burden of cancer 2013. JAMA Oncol. 2015; 1(4): 505-27, CrossRef.
Ma BBY, Hui EP, Chan ATC. Systemic approach to improving treatment outcome in nasopharyngeal carcinoma: Current and future directions. Cancer Sci. 2008; 99(7): 1311-8, CrossRef.
Lee AWM, Ma BBY, Ng WT, Chan ATC. Management of nasopharyngeal carcinoma: current practice and future perspective. J Clin Oncol. 2015; 33(29): 3356-64, CrossRef.
Topalian SL, Taube JM, Anders RA, Pardoll DM. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Publ Gr. 2016; 16(5): 275-87, CrossRef.
Chen L, Han X. Anti–PD-1/PD-L1 therapy of human cancer: past, present, and future. J Clin Invest. 2015; 125(9): 3384-91, CrossRef.
Jain A, Chia WK, Toh HC. Immunotherapy for nasopharyngeal cancer-A review. Chinese Clin Oncol. 2016; 5(2): 22, CrossRef.
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Publ Gr. 2012; 12(4): 252-64, CrossRef.
He J, Hu Y, Hu M, Li B. Development of PD-1/PD-L1 pathway in tumor immune microenvironment and treatment for non-small cell lung cancer. Nat Publ Gr. 2015; 5: 13110, CrossRef.
Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015; 14(4): 847-56, CrossRef.
Waki K, Yamada T, Yoshiyama K, Terazaki Y, Sakamoto S, Matsueda S, et al. PD-1 expression on peripheral blood T-cell subsets correlates with prognosis in non-small cell lung cancer. Cancer Sci. 2014; 105(10): 1229-35, CrossRef.
MacFarlane AW, Jillab M, Plimack ER, Hudes GR, Uzzo RG, Litwin S, et al. PD-1 expression on peripheral blood cells increases with stage in renal cell carcinoma patients and is rapidly reduced after surgical tumor resection. Cancer Immunol Res. 2014; 2(4): 320-31, CrossRef.
Wang W, Shen G, Wu S, Song S, Ni Y, Suo Z, et al. PD-1 mRNA expression in peripheral blood cells and its modulation characteristics in cancer patients. Oncotarget. 2017; 8(31): 50782-91, CrossRef.
Amatatsu M, Arigami T, Uenosono Y, Yanagita S, Uchikado Y, Kijima Y, et al. Programmed death-ligand 1 is a promising blood marker for predicting tumor progression and prognosis in patients with gastric cancer. Cancer Sci. 2018; 109(3): 814-20, CrossRef.
Li YF, Ding JW, Liao LM, Zhang ZL, Liao SS, Wu Y, et al. Expression of programmed death ligand-1 predicts poor outcome in nasopharyngeal carcinoma. Mol Clin Oncol. 2017; 7(3): 378-82, CrossRef.
Huang ZL, Liu S, Wang GN, Zheng SH, DIng SR, Tao YL, et al. The prognostic significance of PD-L1 and PD-1 expression in patients with nasopharyngeal carcinoma: A systematic review and meta-analysis. Cancer Cell Int. 2019; 19(1): 141, CrossRef.
Zhou Y, Miao J, Wu H, Tang H, Kuang J. PD-1 and PD-L1 expression in 132 recurrent nasopharyngeal carcinoma : the correlation with anemia and outcomes. Oncotarget. 2017; 8(31): 51210-23, CrossRef.
Hassan SS, Akram M, King EC, Dockrell HM, Cliff JM. PD-1, PD-L1 and PD-L2 gene expression on T-cells and natural killer cells declines in conjunction with a reduction in PD-1 protein during the intensive phase of tuberculosis treatment. PLoS ONE. 2015: 10(9): e0137646, CrossRef.
Zhong J, Chen S, Xu L, Lai J, Liao Z, Zhang T, et al. Lower expression of PD-1 and PD-L1 in peripheral blood from patients with chronic ITP Lower expression of PD-1 and PD-L1 in peripheral blood from patients with chronic ITP. Hematology. 2016; 21(9): 552-7, CrossRef.
Qu Y, Wang D, Yang L, Liu HY, Cui W, Che YQ. Expression and clinical significance of programmed death ligand 1 in nasopharyngeal carcinoma. Mol Clin Oncol. 2018; 9(1): 75-81, CrossRef.
Li J, Huang ZF, Xiong G, Mo HY, Qiu F, Mai HQ, et al. Distribution, characterization, and induction of CD8+regulatory T cells and IL-17-producing CD8+T cells in nasopharyngeal carcinoma. J Transl Med. 2011; 9(1): 189, CrossRef.
Yu J, Wang X, Teng F, Kong L. PD-L1 expression in human cancers and its association with clinical outcomes. Onco Targets Ther. 2016; 9: 5023-39, CrossRef.
Zhang F, Liu Z, Cui Y, Wang G, Cao P. The clinical significance of the expression of costimulatory molecule PD-L1 in nasopharyngeal carcinoma. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2008; 22(9): 408-10, article.
Weber M, Wehrhan F, Baran C, Agaimy A, Büttner-Herold M, Preidl R, et al. PD-L1 expression in tumor tissue and peripheral blood of patients with oral squamous cell carcinoma. Oncotarget. 2017; 8(68): 112584-97, CrossRef.
Fang W, Zhang J, Hong S, Zhan J. EBV-driven LMP1 and IFN-γ up-regulate PD-L1 in nasopharyngeal carcinoma : Implications for oncotargeted therapy. Oncotarget. 2014; 5(23): 12189-202, CrossRef.
DOI: https://doi.org/10.21705/mcbs.v4i3.143
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