Background. Programmed death 1 (PD-1) is a co-receptor which is located at the surface of cells like natural killer, monocytes, T and B cells. It has two ligands including programmed death ligand-1 (PD-L1) and ligand-2 (PD-L2). T cell functions are inhibited by activation of PD-1/PD-L1 pathway and this pathway is used by viruses and some tumor cells in order to escape from immune eradication. In our study we evaluated PD-L1 expression in the tissue specimens of patients with Wilms tumor, neuroblastoma and other renal tumors. Methods. Totally 60 patients who were followed up at Gazi University Hospital with the diagnosis of neuroblastoma, Wilms tumor and other renal tumors were included. PD-L1 expression was examined in tumor samples of the patients. Results. Positive staining with PD-L1 was detected only in two male patients. Both of them had neuroblastoma and advanced stage disease. None of the patients with Wilms tumor and other renal tumors had positive PD-L1 staining. Conclusions. Unlike adult tumors, PD-L1 expression is not common in childhood tumors due to differences in immune system between children and adults. Further studies are needed to establish the importance and effects of PD-1/PD-L1 pathway in pediatric tumors.
___
1. Keir M, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Ann Rev Immunol 2008; 26: 677-704.
2. Latchman Y, Wood C, Chernova T, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol 2001; 2: 261-268.
3. Tseng S, Otsuji M, Gorski K, et al. B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells. J Exp Med 2001; 193: 839-845.
4. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA 2002; 99: 12293-12297.
5. Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366: 2443- 2454.
6. Herbst RS, Soria JS, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 2014; 515: 563-567.
7. van Dam LS, de Zwart VM, Meyer-Wentrup FA. The role of programmed cell death-1 (PD-1) and its ligands in pediatric cancer. Pediatr Blood Cancer 2014; 62: 190-197.
8. Aksoylar S, Varan A, Vergin C, et al. Treatment of high-risk neuroblastoma: National protocol results of the Turkish Pediatric Oncology Group. J Can Res Ther 2017; 13: 284-290.
9. Shimada H, Ambros IM, Dehner LP, et al. The International Neuroblastoma Pathology Classification (the Shimada system). Cancer 1999; 86: 364-372.
10. Bertolini G, Bergamaschi L, Ferrari A, et al. PD-L1 assessment in pediatric rhabdomyosarcoma: a pilot study. BMC Cancer 2018; 18: 652.
11. 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: 1021-1034.
12. Afreen S, Dermine S. The immunoinhibitory B7-H1 molecule as a potential target in cancer: killing many birds with one stone. Hematol Oncol Stem Cell Ther 2014; 7: 1-17.
13. Ohigashi Y, Sho M, Yamada Y, et al. Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res 2005; 11: 2947- 2953.
14. Routh JC, Ashley RA, Sebo TJ, et al. B7-H1 expression in Wilms tumor: correlation with tumor biology and diseaser currence. J Urol 2008; 179: 1954-1960.
15. Uehara S, Nakahata K, Kawatsu M, et al. The PD-L1 expression increases after consecutive multimodal therapeies in neuroblastoma. Pediatr Blood Cancer 2015; 62: S334.
16. Chowdhury F, Dunn S, Mitchell S, Mellows T, Ashton-Key M, Gray JC. PD-L1 and CD8+ PD1+ lymphocytes exist as targets in the pediatric tumor microenvironment for immunomodulatory therapy. Oncoimmunology 2015; 4: e1029701.
17. Aoki T, Hino M, Koh K, et al. Low frequency of programmed death ligand 1 expression in pediatric cancers. Pediatr Blood Cancer 2016; 63: 1461-1464.
18. Pinto N, Park JR, Murphy E, et al. Patterns of PD1,PD-L1 and PD-L2 expression in pediatric solid tumors. Pediatr Blood Cancer 2017; 64: e26613.
19. Saletta F, Vilain RE, Gupta AK, et al. Programmed Death-Ligand 1 expression in a large cohort of pediatric patients with solid tumor and association with clinicopathologic features in neuroblastoma. JCO Precis Oncol 2017; 1: 1-12.
20. Majzner RG, Simon JS, Grosso JF, et al. Assessment of programmed death-ligand 1 expression and tumor-associated immune cells in pediatric cancer tissues. Cancer 2017; 123: 3807-3815.
21. Dondero A, Pastorino F, Della Chiesa M, et al. PD-L1 expression in metastatic neuroblastoma as an additional mechanism for limiting immune surveillance. Oncoimmunology 2015; 5: e1064578.
22. Altungoz O, Aygun N, Tumer S, Ozer E, Olgun N, Sakizli M. Correlation of modified Shimada classification with MYCN and 1p36 status detected by fluorescence in situ hybridization in neuroblastoma. Cancer Genet Cytogenet 2007; 172: 113-119.
23. Madore J, Vilain RE, Menzies AM, et al. PDL1 expression in melanoma shows marked heterogeneity within and between patients: implications for anti PD-1/PD-L1 clinical trials. Pigment Cell Melanoma Res 2015; 28: 245-253.
24. Taube JM, Klein A, Brahmer JR, et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti PD-1 therapy. Clin Cancer Res 2014; 20: 5064-5074.
25. McLaughlin J, Han G, Schalper KA, et al. Quantitative assessment of the heterogeneity of PD-L1 expression in non-small-cell lung cancer. JAMA Oncol 2016; 2: 46-54.
26. Watson IR, Takahashi K, Futreal PA, Chin L. Emerging patterns of somatic mutations in cancer. Nat Rev Genet 2013; 14: 703-718.