The mRNA Expression Profile of PD-1 and PD-L1 in Peripheral Blood of Colorectal Cancer Patients
Background: Immunotherapy using immune checkpoint inhibitors has currently emerged as an effective treatment for a subset of colorectal cancer (CRC) patients. The roles of PD-1 and PD-L1 expression levels in peripheral blood to predict patient’s response to immune checkpoint inhibitors are not well established. Therefore, we analyzed PD-1 and PD-L1 mRNA expression levels of peripheral blood in Indonesian CRC patients and explored the association with the clinicopathological features.
Methods: Peripheral blood of 25 CRC patients and 10 healthy individuals were collected in Dharmais Hospital-National Cancer Center from 2017 to 2018. PD-1 and PD-L1 mRNA expression levels were analyzed using real time PCR. The associations with clinicopathological variables were analyzed with fisher-exact test or chi square test.
Results: PD-1 mRNA expression levels were significantly lower in CRC patients compared to healthy individuals (HI) (mean: 0.0015 ± 0.0013 and 0.017 ± 0.010 respectively, p < 0.001). Although PD-L1 mRNA expression levels were lower in CRC patients, the difference was not statistically significant (mean in CRC and HI: 0.021 ± 0.013 and 0.034 ± 0.028 respectively, p = 0.125). The expression of PD-L1 was higher in CRC females compared to males (p = 0.03). The expression levels of PD-L1 were not associated with different ages (p = 0.673), stages (p = 0.298), histological type of colorectal cancer (p=0.852), patient status (p = 1.000), and body mass index (p = 0.514).
Conclusions: The mRNA expression levels of PD-1 and PD-L1 were lower in CRC patients compared to healthy controls. Expression of PD-L1 were correlated with sex, but not correlated with ages, stages, histological type of CRC, patient status, and body mass index.
International Agency of Research on Cancer (IARC). Latest global cancer data : Cancer burden rises to 18.1 million new cases and 9.6 million cancer deaths in 2018 [Internet]. Geneva: IARC; 12 Sep 2018 [cited 2019 April 15]. Available from: https://www.who.int/cancer/PRGlobocanFinal.pdf
DeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64(4):252–71.
Augestad KM, Merok MA, Ignatovic D. Tailored treatment of colorectal cancer: Surgical, molecular, and genetic considerations. Clin Med Insights Oncol. 2017;11.
Topalian SL, Taube JM, Anders RA, Pardoll DM. in cancer therapy. Nat Publ Gr. 2016;16(5):275–87.
Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and Its Ligands in Tolerance and Immunity. Annu Rev Immunol. 2008;26(1):677–704.
Francisco LM, Salinas VH, Brown KE, Vanguri VK, Freeman GJ, Kuchroo VK, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009;206(13):3015–29.
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;(July):1–9.
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Publ Gr [Internet]. 2012;12(4):252–64. Available from: http://dx.doi.org/10.1038/nrc3239.
Valentini AM, Pinto F Di, Cariola F, Guerra V, Caruso ML, Pirrelli M. PD-L1 expression in colorectal cancer defines three subsets of tumor immune microenvironments. 2018;9(9):8584–96.
Hino R, Kabashima K, Kato Y, Yagi H, Nakamura M, Honjo T, et al. Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer. 2010;116(7):1757–66.
Wu P, Wu D, Li L, Chai Y, Huang J. PD-L1 and survival in solid tumors: A meta-analysis. PLoS One. 2015;10(6):1–15.
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.
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.
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. 2013;2(4):320–31.
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.
Song M, Chen D, Lu B, Wang C, Zhang J, Huang L, et al. PTEN Loss Increases PD-L1 Protein Expression and Affects the Correlation between PD-L1 Expression and Clinical Parameters in Colorectal Cancer. PLoS One. 2013;8(6).
Droeser RA, Hirt C, Viehl CT, Frey DM, Nebiker C, Huber X, et al. Clinical impact of programmed cell death ligand 1 expression in colorectal cancer. Eur J Cancer. 2013;49(9):2233–42.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods. 2001;25(4):402–8.
Gasser M, Grimm M, Nichiporuk E, Bueter M, Lutz J, Lebedeva T, et al. PD-1/PD-L1 expression in colorectal cancer and its implications for apoptosis and tumor immune evasion. Cancer Res. 2006;66(8 Supplement):1118 LP – 1118.
Lee LH, Cavalcanti MS, Segal NH, Hechtman JF, Martin R. Patterns and prognostic relevance of PD-1 and PD-L1 expression in colorectal carcinoma. Mod Pathol. 2016;29(11):1433–42.
Albitar M, Sudarsanam S, Ma W, Jiang S, Chen W, Funari VA, et al. Expression of PD-L1 in colorectal cancer that lack mutations in RAS or TP53 genes. J Clin Oncol. 2017;35(15_suppl):e14500–e14500.
Rosenbaum MW, Bledsoe JR, Morales-oyarvide V, Huynh TG, Mino-kenudson M. PD-L1 expression in colorectal cancer is associated with microsatellite instability , BRAF mutation, medullary morphology and cytotoxic tumor-infiltrating lymphocytes. Mod Pathol. 2016;1–9.
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;8454.
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;1–15.
Goltz D, Gevensleben H, Dietrich J, Dietrich D. Pd-l1 (CD274) promoter methylation predicts survival in colorectal cancer patients. Oncoimmunology. 2017;6(1):1–4.
Bae SU, Jeong WK, Baek SK, Kim NK, Hwang I. Prognostic impact of programmed cell death ligand 1 expression on long-term oncologic outcomes in colorectal cancer. Oncol Lett. 2018;16(4):5214–22.
Koppel C, Schwellenbach H, Zielinski D, Eckstein S, Martin-Ortega M, D’Arrigo C, et al. Optimization and validation of PD-L1 immunohistochemistry staining protocols using the antibody clone 28-8 on different staining platforms. Mod Pathol. 2018;31(11):1630–44.
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