Browse > Article
http://dx.doi.org/10.4142/jvs.2021.22.e75

Evaluation of circulating PD-1 and PD-L1 as diagnostic biomarkers in dogs with tumors  

Song, Doo-Won (Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University)
Ro, Woong-Bin (Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University)
Park, Hee-Myung (Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University)
Publication Information
Journal of Veterinary Science / v.22, no.5, 2021 , pp. 75.1-75.10 More about this Journal
Abstract
Background: Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have important roles in tumor evasion of the immune system. Objectives: This study aimed to assess the diagnostic utility of circulating PD-1 and PD-L1 levels in healthy dogs and dogs with tumors. Methods: Circulating PD-1 and PD-L1 levels in the serum of 71 dogs with tumors were compared with those of 52 healthy dogs by performing enzyme-linked immunosorbent assay (ELISA). Results: The ELISA results revealed higher circulating PD-1 and PD-L1 levels in dogs with tumors (2.9 [2.2-3.7] ng/mL; median [IQR] and 2.4 [1.4-4.4] ng/mL, respectively) than in healthy dogs (2.4 [1.9-3.0] ng/mL; p = 0.012 and 1.4 [0.9-2.1] ng/mL; p < 0.001, respectively). Especially, there was a significant difference in circulating PD-1 levels between healthy dogs and dogs with malignant epithelial tumors (2.4 [1.9-3.0] ng/mL and 3.1 [2.6-4.4] ng/mL, respectively; p < 0.01). In addition, there was a significant difference in circulating PD-L1 levels between healthy dogs and dogs with lymphomas (1.4 [0.9-2.1] ng/mL and 2.7 [1.6-5.8] ng/mL, respectively; p < 0.001). Conclusion: This study indicates that circulating PD-1 and PD-L1 have potential as tumor diagnostic biomarkers in dogs with tumors.
Keywords
Dog; tumor; biomarker; programmed cell death protein; ligand;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443-2454.   DOI
2 Schiffman JD, Breen M. Comparative oncology: what dogs and other species can teach us about humans with cancer. Philos Trans R Soc Lond B Biol Sci. 2015;370(1673):20140231.   DOI
3 Adams VJ, Evans KM, Sampson J, Wood JL. Methods and mortality results of a health survey of purebred dogs in the UK. J Small Anim Pract. 2010;51(10):512-524.   DOI
4 Chamoto K, Al-Habsi M, Honjo T. Role of PD-1 in immunity and diseases. In: Yoshimura A, editor. Emerging Concepts Targeting Immune Checkpoints in Cancer and Autoimmunity. Basel: Springer International Publishing; 2017, 75-97.
5 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. Sci Rep. 2015;5(1):13110.   DOI
6 Sznol M, Chen L. Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer. Clin Cancer Res. 2013;19(5):1021-1034.   DOI
7 Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 2011;331(6024):1565-1570.   DOI
8 Bian B, Fanale D, Dusetti N, Roque J, Pastor S, Chretien AS, et al. Prognostic significance of circulating PD-1, PD-L1, pan-BTN3As, BTN3A1 and BTLA in patients with pancreatic adenocarcinoma. OncoImmunology. 2019;8(4):e1561120.   DOI
9 Kaunitz GJ, Cottrell TR, Lilo M, Muthappan V, Esandrio J, Berry S, et al. Melanoma subtypes demonstrate distinct PD-L1 expression profiles. Lab Invest. 2017;97(9):1063-1071.   DOI
10 Iacovelli R, Nole F, Verri E, Renne G, Paglino C, Santoni M, et al. Prognostic role of PD-L1 expression in renal cell carcinoma. A systematic review and meta-analysis. Target Oncol. 2016;11(2):143-148.   DOI
11 Zheng Z, Bu Z, Liu X, Zhang L, Li Z, Wu A, et al. Level of circulating PD-L1 expression in patients with advanced gastric cancer and its clinical implications. Chin J Cancer Res. 2014;26(1):104-111.
12 Chen Y, Wang Q, Shi B, Xu P, Hu Z, Bai L, et al. Development of a sandwich ELISA for evaluating soluble PD-L1 (CD274) in human sera of different ages as well as supernatants of PD-L1+ cell lines. Cytokine. 2011;56(2):231-238.   DOI
13 Bonomi M, Ahmed T, Addo S, Kooshki M, Palmieri D, Levine BJ, et al. Circulating immune biomarkers as predictors of the response to pembrolizumab and weekly low dose carboplatin and paclitaxel in NSCLC and poor PS: An interim analysis. Oncol Lett. 2019;17(1):1349-1356.
14 D'Incecco A, Andreozzi M, Ludovini V, Rossi E, Capodanno A, Landi L, et al. PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer. 2015;112(1):95-102.   DOI
15 Zhu X, Lang J. Soluble PD-1 and PD-L1: predictive and prognostic significance in cancer. Oncotarget. 2017;8(57):97671-97682.   DOI
16 Takahashi N, Iwasa S, Sasaki Y, Shoji H, Honma Y, Takashima A, et al. Serum levels of soluble programmed cell death ligand 1 as a prognostic factor on the first-line treatment of metastatic or recurrent gastric cancer. J Cancer Res Clin Oncol. 2016;142(8):1727-1738.   DOI
17 Zhou J, Mahoney KM, Giobbie-Hurder A, Zhao F, Lee S, Liao X, et al. Soluble PD-L1 as a biomarker in malignant melanoma treated with checkpoint blockade. Cancer Immunol Res. 2017;5(6):480-492.   DOI
18 Incorvaia L, Badalamenti G, Rinaldi G, Iovanna JL, Olive D, Swayden M, et al. Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in patients with metastatic melanoma? Ther Adv Med Oncol. 2019;11:1758835919848872.   DOI
19 Cheng HY, Kang PJ, Chuang YH, Wang YH, Jan MC, Wu CF, et al. Circulating programmed death-1 as a marker for sustained high hepatitis B viral load and risk of hepatocellular carcinoma. PLoS One. 2014;9(11):e95870.   DOI
20 Sorensen SF, Demuth C, Weber B, Sorensen BS, Meldgaard P. Increase in soluble PD-1 is associated with prolonged survival in patients with advanced EGFR-mutated non-small cell lung cancer treated with erlotinib. Lung Cancer. 2016;100:77-84.   DOI
21 Frigola X, Inman BA, Krco CJ, Liu X, Harrington SM, Bulur PA, et al. Soluble B7-H1: differences in production between dendritic cells and T cells. Immunol Lett. 2012;142(1-2):78-82.   DOI
22 Coy J, Caldwell A, Chow L, Guth A, Dow S. PD-1 expression by canine T cells and functional effects of PD-1 blockade. Vet Comp Oncol. 2017;15(4):1487-1502.   DOI
23 Cheng S, Zheng J, Zhu J, Xie C, Zhang X, Han X, et al. PD-L1 gene polymorphism and high level of plasma soluble PD-L1 protein may be associated with non-small cell lung cancer. Int J Biol Markers. 2015;30(4):e364-e368.
24 Frigola X, Inman BA, Lohse CM, Krco CJ, Cheville JC, Thompson RH, et al. Identification of a soluble form of B7-H1 that retains immunosuppressive activity and is associated with aggressive renal cell carcinoma. Clin Cancer Res. 2011;17(7):1915-1923.   DOI
25 Rossille D, Gressier M, Damotte D, Maucort-Boulch D, Pangault C, Semana G, et al. High level of soluble programmed cell death ligand 1 in blood impacts overall survival in aggressive diffuse large B-Cell lymphoma: results from a French multicenter clinical trial. Leukemia. 2014;28(12):2367-2375.   DOI
26 Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015;14(4):847-856.   DOI
27 Li N, Zhou Z, Li F, Sang J, Han Q, Lv Y, et al. Circulating soluble programmed death-1 levels may differentiate immune-tolerant phase from other phases and hepatocellular carcinoma from other clinical diseases in chronic hepatitis B virus infection. Oncotarget. 2017;8(28):46020-46033.   DOI
28 Shi MH, Xing YF, Zhang ZL, Huang JA, Chen YJ. Effect of soluble PD-L1 released by lung cancer cells in regulating the function of T lymphocytes. Zhonghua Zhong Liu Za Zhi. 2013;35(2):85-88.
29 Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018-2028.   DOI
30 Kloten V, Lampignano R, Krahn T, Schlange T. Circulating tumor cell PD-L1 expression as biomarker for therapeutic efficacy of immune checkpoint inhibition in NSCLC. Cells. 2019;8(8):809.   DOI
31 Shosu K, Sakurai M, Inoue K, Nakagawa T, Sakai H, Morimoto M, et al. Programmed cell death ligand 1 expression in canine cancer. In Vivo. 2016;30(3):195-204.
32 Ruf M, Moch H, Schraml P. PD-L1 expression is regulated by hypoxia inducible factor in clear cell renal cell carcinoma. Int J Cancer. 2016;139(2):396-403.   DOI
33 Maekawa N, Konnai S, Okagawa T, Nishimori A, Ikebuchi R, Izumi Y, et al. Immunohistochemical analysis of PD-L1 expression in canine malignant cancers and PD-1 expression on lymphocytes in canine oral melanoma. PLoS One. 2016;11(6):e0157176.   DOI
34 Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793-800.   DOI
35 Miyoshi H, Kiyasu J, Kato T, Yoshida N, Shimono J, Yokoyama S, et al. PD-L1 expression on neoplastic or stromal cells is respectively a poor or good prognostic factor for adult T-cell leukemia/lymphoma. Blood. 2016;128(10):1374-1381.   DOI
36 Zhang M, Sun H, Zhao S, Wang Y, Pu H, Wang Y, et al. Expression of PD-L1 and prognosis in breast cancer: a meta-analysis. Oncotarget. 2017;8(19):31347-31354.   DOI
37 Wang L, Wang H, Chen H, Wang WD, Chen XQ, Geng QR, et al. Serum levels of soluble programmed death ligand 1 predict treatment response and progression free survival in multiple myeloma. Oncotarget. 2015;6(38):41228-41236.   DOI
38 Maekawa N, Konnai S, Ikebuchi R, Okagawa T, Adachi M, Takagi S, et al. Expression of PD-L1 on canine tumor cells and enhancement of IFN-γ production from tumor-infiltrating cells by PD-L1 blockade. PLoS One. 2014;9(6):e98415.   DOI
39 Zhang M, Dong Y, Liu H, Wang Y, Zhao S, Xuan Q, et al. The clinicopathological and prognostic significance of PD-L1 expression in gastric cancer: a meta-analysis of 10 studies with 1,901 patients. Sci Rep. 2016;6(1):37933.   DOI
40 Chiarucci C, Cannito S, Daffina MG, Amato G, Giacobini G, Cutaia O, et al. Circulating levels of PD-L1 in mesothelioma patients from the NIBIT-MESO-1 study: correlation with survival. Cancers (Basel). 2020;12(2):361.   DOI