State of PD-L1 and PD-1 screening and therapy in NSCLC
Abstract
Lung cancer is still the leading cause of death among all malignancies worldwide. The development of targeted therapies against driver mutations such as EGFR, ALK1, ROS1 and BRAF have led to a significant improvement in patient progression free survival and to a benefit in quality of life of patients suffering from advanced and metastasized non-small cell lung cancer. But since these genetic aberrations are found only in a small subset of lung cancer more globally directed therapeutic approaches are needed to address the therapeutic dilemma of this highly diverse disease. For a long time, it is known that lung cancer is a so called immunogenic disease, i. e. it often evokes a host immune response. Likewise, lung cancers are also developing mechanisms to escape these anti-cancerous immune reactions. One immunogenic axis is that of PD1 and PD-L1. In investigation of this activation-deactivation chain involving lymphocytes, tumor cells but also stromal fibroblasts and macrophages new humanized antibodies have been developed and approved for the treatment of non-small cell lung cancer (NSCLC). Clinical trials have shown effectiveness of these agents, but a valid and reproducible predictive marker has not been found so far. Here we review the current literature on the PD1/PD-L1 axis in NSCLC, its biological function on histological subtype. Together with meta-analytic data performed for this review and results from our own investigations we also give a comprehensive outlook on future developments considering predictive testing and therapeutic options.
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References
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1. Coley WB. The Treatment of Malignat Tumors By Repeated Inoculations of Erysipelas: With A Report of Ten Original Cases. The American Journal of the Medical Sciences. 1893;105:487–510.
2. Ehrlich P. Ueber den jetzigen stand der karzinomforschung 1908.
3. van der Bruggen P, Traversari C, Chomez P, Lurquin C, Plaen E de, van den Eynde B, et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science (New York, N.Y.). 1991;254:1643–7.
4. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74. doi:10.1016/j.cell.2011.02.013.
5. Leach DR, Krummel MF, Allison JP. Enhancement of Antitumor Immunity by CTLA-4 Blockade. Science. 1996;271:1734. doi:10.1126/science.271.5256.1734.
6. Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. The EMBO journal. 1992;11:3887.
7. Liang SC, Latchman YE, Buhlmann JE, Tomczak MF, Horwitz BH, Freeman GJ, Sharpe AH. Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses. European journal of immunology. 2003;33:2706–16. doi:10.1002/eji.200324228.
8. Agata Y, Kawasaki A, Nishimura H, Ishida Y, Tsubat T, Yagita H, Honjo T. Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. International Immunology. 1996;8:765–72. doi:10.1093/intimm/8.5.765.
9. Okazaki T, Maeda A, Nishimura H, Kurosaki T, Honjo T. PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine. Proceedings of the National Academy of Sciences. 2001;98:13866–71. doi:10.1073/pnas.231486598.
10. Parry RV, Chemnitz JM, Frauwirth KA, Lanfranco AR, Braunstein I, Kobayashi SV, et al. CTLA-4 and PD-1 Receptors Inhibit T-Cell Activation by Distinct Mechanisms. Molecular and Cellular Biology. 2005;25:9543–53. doi:10.1128/mcb.25.21.9543-9553.2005.
11. Sheppard KA, Fitz LJ, Lee JM, Benander C, George JA, Wooters J, et al. PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3zeta signalosome and downstream signaling to PKCtheta. FEBS letters. 2004;574:37–41. doi:10.1016/j.febslet.2004.07.083.
12. Vibhakar R, Juan G, Traganos F, Darzynkiewicz Z, Finger LR. Activation-Induced Expression of Human Programmed Death-1 Gene in T-Lymphocytes. Experimental Cell Research. 1997;232:25–8. doi:10.1006/excr.1997.3493.
13. Zak KM, Kitel R, Przetocka S, Golik P, Guzik K, Musielak B, et al. Structure of the Complex of Human Programmed Death 1, PD-1, and Its Ligand PD-L1. Structure. 2015;23:2341–8. doi:10.1016/j.str.2015.09.010.
14. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annual review of immunology. 2008;26:677–704. doi:10.1146/annurev.immunol.26.021607.090331.
15. Guleria I, Khosroshahi A, Ansari MJ, Habicht A, Azuma M, Yagita H, et al. A critical role for the programmed death ligand 1 in fetomaternal tolerance. The Journal of experimental medicine. 2005;202:231–7. doi:10.1084/jem.20050019.
16. Blank C, Brown I, Marks R, Nishimura H, Honjo T, Gajewski TF. Absence of Programmed Death Receptor 1 Alters Thymic Development and Enhances Generation of CD4/CD8 Double-Negative TCR-Transgenic T Cells. The Journal of Immunology. 2003;171:4574–81. doi:10.4049/jimmunol.171.9.4574.
17. Morita M, Fujino M, Jiang G, Kitazawa Y, Xie L, Azuma M, et al. PD-1/B7-H1 Interaction Contribute to the Spontaneous Acceptance of Mouse Liver Allograft. American Journal of Transplantation. 2010;10:40–6. doi:10.1111/j.1600-6143.2009.02859.x.
18. Ansari MJI, Salama AD, Chitnis T, Smith RN, Yagita H, Akiba H, et al. The Programmed Death-1 (PD-1) Pathway Regulates Autoimmune Diabetes in Nonobese Diabetic (NOD) Mice. The Journal of Experimental Medicine. 2003;198:63–9. doi:10.1084/jem.20022125.
19. Nishimura H, Okazaki T, Tanaka Y, Nakatani K, Hara M, Matsumori A, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science (New York, N.Y.). 2001;291:319–22.
20. Das S, Suarez G, Beswick EJ, Sierra JC, Graham DY, Reyes VE. Expression of B7-H1 on Gastric Epithelial Cells: Its Potential Role in Regulating T Cells during Helicobacter pylori Infection. The Journal of Immunology. 2006;176:3000–9. doi:10.4049/jimmunol.176.5.3000.
21. Yao S, Wang S, Zhu Y, Luo L, Zhu G, Flies S, et al. PD-1 on dendritic cells impedes innate immunity against bacterial infection. Blood. 2009;113:5811–8. doi:10.1182/blood-2009-02-203141.
22. Iwai Y, Terawaki S, Ikegawa M, Okazaki T, Honjo T. PD-1 inhibits antiviral immunity at the effector phase in the liver. The Journal of experimental medicine. 2003;198:39–50. doi:10.1084/jem.20022235.
23. Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH, et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature. 2006;439:682–7. doi:10.1038/nature04444.
24. Trautmann L, Janbazian L, Chomont N, Said EA, Gimmig S, Bessette B, et al. Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nature medicine. 2006;12:1198–202. doi:10.1038/nm1482.
25. Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999;5:1365–9. doi:10.1038/70932.
26. 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. Nature medicine. 2002;8:793–800. doi:10.1038/nm730.
27. Velcheti V, Schalper KA, Carvajal DE, Anagnostou VK, Syrigos KN, Sznol M, et al. Programmed death ligand-1 expression in non-small cell lung cancer. Laboratory investigation; a journal of technical methods and pathology. 2014;94:107–16. doi:10.1038/labinvest.2013.130.
28. Gong A-Y, Zhou R, Hu G, Li X, Splinter PL, O'Hara SP, et al. MicroRNA-513 Regulates B7-H1 Translation and Is Involved in IFN-γ-Induced B7-H1 Expression in Cholangiocytes. The Journal of Immunology. 2009;182:1325–33. doi:10.4049/jimmunol.182.3.1325.
29. Konishi J, Yamazaki K, Azuma M, Kinoshita I, Dosaka-Akita H, Nishimura M. B7-H1 Expression on Non-Small Cell Lung Cancer Cells and Its Relationship with Tumor-Infiltrating Lymphocytes and Their PD-1 Expression. Clinical Cancer Research. 2004;10:5094–100. doi:10.1158/1078-0432.ccr-04-0428.
30. Schmidt LH, Kummel A, Gorlich D, Mohr M, Brockling S, Mikesch JH, et al. PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups. PLoS One. 2015;10:e0136023. doi:10.1371/journal.pone.0136023.
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Published
2018-04-11
How to Cite
BRUEHL, Frido et al.
State of PD-L1 and PD-1 screening and therapy in NSCLC.
Diagnostic Pathology, [S.l.], v. 4, n. 1, apr. 2018.
ISSN 2364-4893.
Available at: <https://www.diagnosticpathology.eu/content/index.php/dpath/article/view/262>. Date accessed: 19 apr. 2024.
doi: https://doi.org/10.17629/www.diagnosticpathology.eu-2018-4:262.
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Section
Review Articles
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