#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

The Role of PD-1/PD-L1 Signaling Pathway in Antitumor Immune Response


Authors: P. Zatloukalová;  M. Pjechová;  S. Babčanová;  T. R. Hupp;  B. Vojtěšek
Authors‘ workplace: Regionální centrum aplikované molekulární onkologie, Masarykův onkologický ústav, Brno
Published in: Klin Onkol 2016; 29(Supplementum 4): 72-77
Category: Review
doi: https://doi.org/10.14735/amko20164S72

Overview

Background:
Correct function of the immune system depends on close cooperation between stimulation and inhibition signals, which protect an organism from outside microorganisms and other agents, but also protects healthy tissues against possible self-destructing attacks of the immune system. However, the inhibitory mechanisms can be abused by cancer cells that evade immune responses and, in fact, they help develop cancer. Therefore, one of the characteristics of cancer cells is the ability to evade immune recognition. Immunotherapy is a treatment method that stimulates the immune system to fight cancer. The checkpoints of the immune system can be considered as effective and specific therapeutic targets. Programmed cell death signaling pathway (PD-1/PD-L1) is one of the most discussed inhibition pathways in recent years. Blockage of PD-1/PD-L1 interaction restores mechanisms of immune response and increases antitumor immune activity. Monoclonal antibodies blocking PD-1 receptor or its ligand PD-L1 have already shown clinical efficacy. However, it is important to carry out research to explore the mechanisms of PD-1/PD-L1 pathway to find new factors, which influence its activity and, of course, to illuminate the variability of this pathway which naturally originates in the diversity of the tumor milieu. Obtained results could be utilized to achieve maximal anticancer effect after inhibition of PD-1/PD-L1 signaling pathway useful in clinical practice.

Aim:
The aim of the article is to summarize current knowledge about PD-1/PD-L1 signaling pathway and to discuss its role in antitumor immune response.

Key words:
programmed cell death pathway – tumor escape – PD-1 – PD-L1 – CD274

This work was supported by the project MEYS – NPS I – LO1413.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
13. 6. 2016

Accepted:
4. 8. 2016


Sources

1. Šťastný M, Říhová B. Únikové strategie nádorů pozornosti imunitního systému. Klin Onkol 2015; 28 (Suppl 4): 4S28–4S37. doi: 10.14735/amko20154S28.

2. Melichar B, Nash MA, Lenzi R et al. Expression of costimulatory molecules CD80 and CD86 and their receptors CD28, CTLA-4 on malignant ascites CD3+ tumour-infiltrating lymphocytes (TIL) from patients with ovarian and other types of peritoneal carcinomatosis. Clin Exp Immunol 2000; 119 (1): 19–27.

3. Barber DL, Wherry EJ, Masopust D et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 2006; 439 (7077): 682–687.

4. Zhang X, Schwartz JC, Guo X et al. Structural and functional analysis of the costimulatory receptor programmed death-1. Immunity 2004; 20 (3): 337–347.

5. Riley JL. PD-1 signaling in primary T-cells. Immunol Rev 2009; 229 (1): 114–125. doi: 10.1111/j.1600065X.2009.00767.x.

6. Keir ME, Butte MJ, Freeman GJ et al. PD-1 and its ligands in tolerance and immunity. J Annu Rev Immunol 2008; 26: 677–704. doi: 10.1146/annurev.immunol.26.021607.090331.

7. Francisco LM, Salinas VH, Brown K et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med 2009; 206 (13): 3015–3029. doi: 10.1084/jem.20090847.

8. Raimondi G, Shufesky WJ, Tokita DM et al. Regulated compartmentalization of programmed cell death-1 discriminates CD4+CD25+ rating regulatory T cells from activated T cells. J Immunol 2006; 176 (5): 2808–2816.

9. Chemnitz JM, Parry RV, Nichols KE et al. SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J Immunol 2004; 173 (2): 945–954.

10. Dong H, Zhu G, Tamada K et al. B7-H1 determines accumulation and deletion of intrahepatic CD8 (+) T lymphocytes. Immunity 2004; 20 (3): 327–336.

11. Chen L. Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol 2004; 4 (5): 336–347.

12. Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol 2008; 8 (6): 467–477. doi: 10.1038/nri2326.

13. Butte MJ, Keir ME, Phamduy TB et al. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity 2007; 27 (1): 111–122.

14. Yang J, Riella LV, Chock S et al. The novel costimulatory programmed death ligand 1/B7.1 pathway is functional in inhibiting alloimmune responses in vivo. J Immunol 2011; 187 (3): 1113–1119. doi: 10.4049/jimmunol.1100056.

15. Xiao Y, Yu S, Zhu B et al. RGMb is a novel binding partner for PD-L2 and its engagement with PD-L2 promotes respiratory tolerance. J Exp Med 2014; 211 (5): 943–959. doi: 10.1084/jem.20130790.

16. He J, Hu Y, Hu M et al. Development of PD-1/PD-L1 pathway in tumor immune microenvironment and treatment for non-small cell lung cancer. Sci Rep 2015; 5: 13110. doi: 10.1038/srep13110.

17. Dong H, Strome SE, Salomao DR et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002; 8 (8): 793–800.

18. Ansell SM, Lesokhin AM, Borrello I et al. PD-1 Blockade with nivolumab in relapsed or refractory Hodgkin‘s lymphoma. N Engl J Med 2015; 372 (4): 311–319. doi: 10.1056/NEJMoa1411087.

19. Curiel TJ, Wei S, Dong H et al. Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 2003; 9 (5): 562–567.

20. Patsoukis N, Sari D, Boussiotis VA. PD-1 inhibits T cell proliferation by upregulating p27 and p15 and suppressing Cdc25A. Cell Cycle 2012; 11 (23): 4305–4309. doi: 10.4161/cc.22135.

21. Staron MM, Gray SM, Marshall HD et al. The transcription factor FoxO1 sustains expression of the inhibitory receptor PD-1 and survival of antiviral CD8+ T cells during chronic infection. Immunity 2014; 41 (5): 802–814. doi: 10.1016/j.immuni.2014.10.013.

22. Patsoukis N, Bardhan K, Chatterjee P et al. PD-1 alters T-cell metabolic reprogramming by inhibiting glycolysis and promoting lipolysis and fatty acid oxidation. Nat Commun 2015; 6: 6692. doi: 10.1038/ncomms7692.

23. Amarnath S, Mangus CV, Wang JC et al. The PDL1-PD1 axis converts human TH1 cells into regulatory T cells. Sci Transl Med 2011; 3 (111): 111ra120. doi: 10.1126/scitranslmed.3003130.

24. Wang W, Lau R, Yu D et al. PD1 blockade reverses the suppression of melanoma antigen-specific CTL by CD4+ CD25 (Hi) regulatory T cells. Int Immunol 2009; 21 (9): 1065–1077. doi: 10.1093/intimm/dxp072.

25. Rosenblatt J, Glotzbecker B, Mills H et al. PD-1 blockade by CT-011, anti-PD-1 antibody, enhances ex vivo T-cell responses to autologous dendritic cell/myeloma fusion vaccine. J Immunother 2011; 34 (5): 409–418. doi: 10.1097/CJI.0b013e31821ca6ce.

26. Jiang X, Zhou J, Giobbie-Hurder A et al. The activation of MAPK in melanoma cells resistant to BRAF inhibition promotes PD-L1 expression that is reversible by MEK and PI3K inhibition. Clin Cancer Res 2013; 19 (3): 598–609. doi: 10.1158/1078-0432.CCR-12-2731.

27. Akbay EA, Koyama S, Carretero J et al. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov 2013; 3 (12): 1355–1363. doi: 10.1158/2159-8290.CD-13-0310.

28. Song M, Chen D, Lu B 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): e65821. doi: 10.1371/journal.pone.0065821.

29. Gong W, Song Q, Lu X et al. Paclitaxel induced B7-H1 expression in cancer cells via the MAPK pathway. J Chemother 2011; 23 (5): 295–299.

30. Qin X, Liu C, Zhou Y et al. Cisplatin induces programmed death-1-ligand1 (PD-L1) over-expression in hepatoma H22 cells via Erk/MAPK signaling pathway. Cell Mol Biol (Noisy-le-grand) 2010; 56 (Suppl): OL1366–OL1372.

31. Barsoum IB, Smallwood CA, Siemens DR et al. A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells. Cancer Res 2014; 74 (3): 665–674. doi: 10.1158/0008-5472.CAN-13-0992.

32. Chen L, Gibbons DL, Goswami S et al. Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression. Nat Commun 2014; 5: 5241. doi: 10.1038/ncomms6241.

33. Gong AY, Zhou R, Hu G et al. Cryptosporidium parvum induces B7-H1 expressionin cholangiocytes by down-regulating microRNA-513. J Infect Dis 2010; 201 (1): 160–169. doi: 10.1086/648589.

34. Chinai JM, Janakiram M, Chen F et al. New immunotherapies targeting the PD-1 pathway. Trends Pharmacol Sci 2015; 36 (9): 587–595. doi: 10.1016/j.tips.2015.06.005.

35. Wang WB, Yen ML, Liu KJ et al. Interleukin-25 mediates transcriptional control of PD-L1 via STAT3 in multipotent human mesenchymal stromal cells (hMSCs) to suppress Th17 responses. Stem Cell Reports 2015; 5 (3): 392–404. doi: 10.1016/j.stemcr.2015.07.013.

36. Brahmer JR, Horn L, Gandhi L et al. Nivolumab (anti-PD-1, BMS-936558,ONO-4538) in patients (pts) with advanced non-small-cell lung cancer (NSCLC): survival and clinical activity by subgroup analysis. J Clin Oncol 2014; 32 (Suppl): abstr. 8112.

37. Powles T, Eder JP, Fine GD et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 2014; 515 (7528): 558–562. doi: 10.1038/nature13904.

38. Massard C, Gordon MS, Sharma S et al. Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol 2016; 34 (26): 3119–3129. doi: 10.1200/JCO.2016.67.9761.

39. Larkin J, Chiarion-Sileni V, Gonzales R et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015; 373 (1): 23–34. doi: 10.1056/NEJMoa1504030.

40. Teixidó C, Karachaliou N, González-Cao M et al. Assays for predicting and monitoring responses to lung cancer immunotherapy. Cancer Biol Med 2015; 12 (2): 87–95. doi: 10.7497/j.issn.2095-3941.2015.0019.

Labels
Paediatric clinical oncology Surgery Clinical oncology

Article was published in

Clinical Oncology

Issue Supplementum 4

2016 Issue Supplementum 4

Most read in this issue
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#